Formulations of triazolone compounds and uses thereof

Abstract

Disclosed herein is a pharmaceutical composition comprising (a) 2-(3'-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1'-biphenyl]-3-yl)acetic acid: (Compound 1), or a pharmaceutically acceptable salt thereof; a diluent; a disintegrant; and a lubricant.

Description

WSGR Docket No. 53238-724.601FORMULATIONS OF TRIAZOLONE COMPOUNDS AND USES THEREOF CROSS-REFERENCE

[0001] This application claims the benefit of U. S. Provisional Application Serial No. 63 / 774,975 filed March 20, 2025; which is hereby incorporated by reference in its entirety.FIELD OF THE DISCLOSURE

[0002] The disclosure relates to a pharmaceutical formulation of triazolones, or pharmaceutically acceptable salts thereof, useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The disclosure is further directed to methods of using the pharmaceutical formulation for treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers.BACKGROUND

[0003] While tremendous strides have been made in the treatment of various cancers, in many cases, cancer treatment continues to be a matter of administering one or more anti-cancer agents that are marginally less chemotoxic to healthy cells than they are to the cancer in question. In recognition of this problem, there has been substantial research effort aimed at identifying, understanding and taking advantage of phenotypical behavior peculiar to certain cancer cells. It has long been observed that most cancer cell types generate energy for cellular processes through aerobic glycolysis rather than through oxidative phosphorylation as found in the normal cell. This process, which became known as the “Warburg effect”, is highly energy inefficient and requires cancer cell mitochondria to resort to glucose fermentation to make up the energy deficit. Since perhaps the mid-1990’s researchers have sought to identify methods of treating cancer that take advantage of the “Warburg effect” and associated aspects of cancer cell mitochondrial metabolism. See, for example, Wang, et al., Small mitochondrial-targeting molecules as anti-cancer agents, Mol. Aspects Med. 2010 February; 31(1): 75-92. Samudio, et al., J. Clin. Invest. 120: 142-156 (2010), disclosed that in certain leukemia cell lines “mitochondrial uncoupling - the continuing reduction of oxygen without ATP synthesis - has recently been shown in leukemic cells to circumvent the ability of oxygen to inhibit glycolysis, and may promote the metabolic preference for glycolysis by shifting from pyruvate oxidation to fatty acid oxidation (FAO).” Samudio, et. al., also provided data indicating that inhibition of FAO could sensitize human leukemia cells to apoptosis, and further that inhibition of FAO may prove useful in the treatment of leukemia. PPARa is known to be an important regulator of fatty acid oxidation. See Pyper, et al., Nucl. Recept. Signal.8:e002., e002 (2010). It has been reported that the expression of the PPARa gene can be higher in human chronic lymphocyte leukemia (CLL) making this cancer type sensitive to therapies aimed at reducing FAO (Samudio etal., J. Clin. Invest. 120: 142-156 (2010)). This effect may generalize to several cancer types. For example, ovarian cancer and breast cancer (Linher-Melville et al., 2011, BMC,WSGR Docket No. 53238-724.6014; 11:56), thrive in an adipose rich environment and as a result can be negatively impacted by targeted therapies that reduce fatty acid metabolism (Nieman et al., 2011, Nat Med. 2011 Oct 30;17(l 1): 1498-503). Still other cancers that rely on FAO include prostate cancer (Liu, Prostate Cancer Prostatic Dis.2006; 9(3):230-4), colon cancer (Holla et al., 2011, JCB 286(34):30003-30009), pancreatic cancer (Khasawneh et al., 2009, PNAS 106(9):3354-3359) and lung cancer (Zaugg et al., 2011, Genes and Development, 25:1041-1051). GW6471 (Xu etal., Nature 415, 813-817 (2002) and MK-866 (Kehrer et al., Biochem. J. 356, 899-906 (2001) have been identified as antagonists of PPARa. Moreover, MK-866, whose primary activity is as an inhibitor of FLAP, has been disclosed to induce apoptosis in a human chronic lymphocytic leukemia cell line in a FLAP -independent manner; and has also been disclosed to induce apoptosis in prostate and glioblastoma cell lines. It is our belief that in cancers that rely heavily on FAO, antagonism of PPARa by small molecules provides a panoply of anti-cancer treatment opportunities to: reduce or halt proliferation; decrease or reverse immunosupression; enhance apoptosis; and increase susceptibility of cancerous cells to other anti-cancer agents. These cancers include prostate, breast, colon and pancreatic cancer, among others. Chronic myeloid leukemia (CML) is model of hematopoietic stem cell (HSC) disease. In 2008, Ito et al. disclosed evidence linking the loss of promyelocytic leukemia (PML) gene expression with favorable outcomes in CML (Nature, 2008 June 19; 453 (7198) 1072-1078). More recently Ito et al. disclosed that in the PML pathway, loss of PPAR5 and accompanying inhibition of mitochondrial FAO induced loss of hematopoietic stem cell (HSC) maintenance (Nature Medicine, doi:10.1038 / nm.2882). Moreover, Carracedo et al. disclosed that whereas PML expression allowed luminal filling in 3D basement membrane breast cancer, the effect was reversed by inhibition of FAO (J. Clin. Invest. 2012;122(9):3088-3100). This and other evidence supports our view that inhibition of fatty acid oxidation, via antagonism of PPAR’ s (including PPARa), will prove effective in inhibiting asymmetric leukemia stem cell differentiation, and therefore, prove effective in preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers. PPARa antagonists have also been shown to inhibit HCV replication and thereby prove useful in the treatment of HCV infection (Rakic et al., Chem. & Biol. 13, 23-30 (January 2006)). In some embodiments, PPAR modulators have been shown to inhibit viral transcription and replication and thereby prove useful in the treatment of viral diseases (Capeau et al., PPAR Research Volume 2009, Article ID 393408, 2 pages). In some embodiments, PPARa antagonists are useful in the treatment of HIV infection. PPARa antagonists have also been disclosed to be useful in the treatment of metabolic disorders (WO2012 / 027482A2). Metabolic disorders include, but are not limited to diabetes, obesity, metabolic syndrome, impaired glucose tolerance, syndrome X, and cardiovascular disease.WSGR Docket No. 53238-724.601SUMMARY

[0004] Disclosed herein is a pharmaceutical composition comprising: (a) about 20% (w / w) to about 40% (w / w) of 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:(Compound 1), or a pharmaceutically acceptable salt thereof; (b) about 50% (w / w) to about 70% (w / w) of a diluent; (c) about 5% (w / w) to about 15% (w / w) of a disintegrant; and (d) about 0.1% (w / w) to about 2% (w / w) of a lubricant. In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 53%(w / w) and about 67% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 55% (w / w) and about 65% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 63% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 58% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 59% (w / w) and about 61% (w / w). In some embodiments, the diluent comprises a first diluent and a second diluent. In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w). In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w). In some embodiments, the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose. In some embodiments,WSGR Docket No. 53238-724.601the diluent comprises an intra-granular diluent and an extra-granular diluent. In some embodiments, the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose. In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w). In some embodiments, the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate. In some embodiments, the disintegrant comprises an intra-granular disintegrant and an extra-granular disintegrant. In some embodiments, the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium. In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1.5% (w / w). In some embodiments, the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 26% (w / w) and about 34% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 27% (w / w) and about 33% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 29% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 29% (w / w) and about 31% (w / w). In some embodiments,WSGR Docket No. 53238-724.601the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 31% (w / w) and about 32% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 30% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 31% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 32% (w / w). In some embodiments, the Compound 1 is in a free acid form. In some embodiments, the Compound 1 is in a salt form. In some embodiments, the Compound 1 is a sodium salt. In some embodiments, the pharmaceutical composition further comprises a coating layer. In some embodiments, the coating layer comprises an Opadry coating fdm, an Eudragit coating fdm, or methacrylic acid copolymer. In some embodiments, the coating layer comprises pigment, polyvinyl alcohol, Talc, calcium carbonate, and / or sodium lauryl sulfate. In some embodiments, the coating layer is about 1% (w / w) to about 10% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 2% (w / w) to about 8% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 3% (w / w) to about 7% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 4% (w / w) to about 6% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 3% (w / w) to about 4% (w / w) in the pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises: about 31% (w / w) of the Compound 1; about 59% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; and about 0.5% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 30% (w / w) of the Compound 1; about 31% (w / w) of mannitol; about 28% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 28% (w / w) to about 29% (w / w) of the Compound 1; about 29% (w / w) to about 30% (w / w) of mannitol; about 26% (w / w) to about 27% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; about 0.9% (w / w) to about 1% (w / w) of magnesium stearate; and about 3% (w / w) to about 4% (w / w) of the coating layer. In some embodiments, the pharmaceutical composition comprises: about 31% (w / w) to about 32% (w / w) of the Compound 1; about 29% (w / w) to about 30% (w / w) of mannitol; about 28% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1.5% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 28% (w / w) to about 29% (w / w) of the Compound 1; about 27% (w / w) to about 28% (w / w) of mannitol; about 25% (w / w) to about 26% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; about 1% (w / w) to about 1.5% (w / w) of magnesium stearate; and about 7% (w / w) to about 8% (w / w) of the coating layer. In some embodiments, the pharmaceutical composition is a tablet or in a capsule. In some embodiments, the pharmaceutical composition is in a capsule. In some embodiments, the pharmaceutical composition is in a capsule comprisingWSGR Docket No. 53238-724.601hydroxypropyl methylcellulose (HPMC). In some embodiments, the capsule comprises about 25 mg or 100 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the pharmaceutical composition is a tablet. In some embodiments, the pharmaceutical composition is a tablet that is produced through direct compaction. In some embodiments, the pharmaceutical composition is a tablet that is produced through roller compaction. In some embodiments, the tablet comprises about 300 mg or 600 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet comprises about 200 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet is about 500 mg to about 1200 mg. In some embodiments, the tablet is about 700 mg to about 750 mg. In some embodiments, the tablet is about 1000 mg to about 1100 mg. In some embodiments, the pharmaceutical composition is administered orally.

[0005] Disclosed herein is a pharmaceutical composition comprising: (a) about 50% (w / w) to about 70% (w / w) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:(Compound 1), or a pharmaceutically acceptable salt thereof; (b) about 15% (w / w) to about 35% (w / w) of a diluent; (c) about 5% (w / w) to about 15% (w / w) of a disintegrant; and (d) about 0.1% (w / w) to about 2% (w / w) of a lubricant. In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 16% (w / w) and about 34% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 17% (w / w) and about 33% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 18% (w / w) and about 32% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 19% (w / w) and about 31% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 20% (w / w) and about 30% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 21% (w / w) and about 29% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 22% (w / w) and about 28% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 23% (w / w) and about 27% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 24% (w / w) and about 26% (w / w). In some embodiments, the diluent comprises a first diluent and a second diluent. In some embodiments, the amount of the first or second diluent in the pharmaceuticalWSGR Docket No. 53238-724.601composition is between about 5% (w / w) and about 15% (w / w). In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 10% (w / w) and about 15% (w / w). In some embodiments, the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises silicified microcrystalline cellulose. In some embodiments, first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the diluent comprises an intra-granular diluent and an extra-granular diluent. In some embodiments, the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose. In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 10% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w). In some embodiments, the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate. In some embodiments, the disintegrant comprises an intra-granular disintegrant and an extra-granular disintegrant. In some embodiments, the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium. In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1% (w / w). In some embodiments, the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w). In some embodiments,WSGR Docket No. 53238-724.601the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 62% (w / w) and about 63% (w / w). In some embodiments, the Compound 1 is in a free acid form. In some embodiments, the Compound 1 is in a salt form. In some embodiments, the Compound 1 is a sodium salt. In some embodiments, the pharmaceutical composition comprises: about 62% (w / w) to about 63% (w / w) of the Compound 1; about 13% (w / w) to about 14% (w / w) of mannitol; about 12% (w / w) to about 13% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition is a tablet. In some embodiments, the pharmaceutical composition is a tablet that is produced through roller compaction. In some embodiments, the tablet comprises about 300 mg to about 350 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet comprises about 600 mg to about 650 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet is about 500 mg to about 1000 mg. In some embodiments, the tablet is about 500 mg. In some embodiments, the tablet is about 1000 mg. In some embodiments, the pharmaceutical composition is administered orally. In some embodiments, the tablet comprises a colorant. In some embodiments, the colorant comprises a pigment. In some embodiments, the tablet comprises an embossed surface.

[0006] Disclosed herein is a method of treating cancer in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition disclosed herein. In some embodiments, the cancer comprises hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), renal cell carcinoma (RCC), colorectal cancer (CRC), pancreatic cancer (PANC), prostate cancer, nonsmall cell lung cancer (NSCLC), or metastatic castration-resistant prostate cancer (mCRPC). In some embodiments, the method further comprises administering to the subject a second therapy. In some embodiments, the administering comprises administering orally. In some embodiments, the administering comprises administering orally a granule of the pharmaceutical composition, wherein a dispenser comprising a pouch or sachet contains the granule of the pharmaceutical composition.INCORPORATION BY REFERENCE

[0007] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.WSGR Docket No. 53238-724.601DETAILED DESCRIPTION OF THE DISCLOSURE

[0008] In one aspect the disclosure is directed to a compound of Formula IA2Formula Ior a pharmaceutical acceptable salt thereof wherein:Al is phenyl or a 6-membered heteroaromatic ring having 1, 2 or 3 N in the heteroaromatic ring; A2 is selected from A2a or A2bT Het|A2a A2bwherein A2a is phenyl or a 6 membered heteroaromatic ring having 1, 2 or 3 N in the heteroaromatic ring, andA2b is a 5 membered heteroaromatic ring having 1, 2 or 3 heteroatoms independently selected from O, S andN;X is selected from the group consisting of -(CH2)m-, -(CH2)m-O-(CH2)n-, -(CH2)m-NH-(CH2)n-, -(CH2)m-S(=O)o-(CH2)n-, optionally mono- or di-substituted with halogen, wherein m and n are independently 0, 1, 2, 3 or 4, and each o is independently 0, 1 or 2;Y is O or S;R1and R2are each independently selected from the group consisting of:(a) hydrogen,(b) halogen,(c) CN,(d) CF3,(e) -Ci-ealkyl,(f) -C1-6alkyl-C(=O)OH,(g) -O-(R7),(h) -S(=O)oR7,(i) -N(R7)(R8),(j) -N(R7)-C(=O)-(R8),(k) -N(R7)-C(=O)-O-(R8),(l) -N(R7)S(=O)2(R8),(m) -Ck.,, cycloalkyl.WSGR Docket No. 53238-724.601(n) -C(=O)(R7),(o) aryl,(p) heteroaryl,(q) -OC(=O)N(R7)(R8),(r) -S(=O)2N(R7)(R8),(s) -C(=O)N(R7)(R8), and(t) -C(R7)(R8)OH,wherein the alkyl portion of choices (e) and (f), and the cycloalkyl portion of choice (m) are optionally substituted with halogen, andwherein the aryl of choice (o) and the heteroaryl of choice (p) are optionally mono- or di-substituted with substituents selected from halogen, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, Ck,, cycloalkyl. C3-ecycloalkoxy, -NH(Ci. ealkyl), -NH(C3-ecycloalkyl), -N(Ci-ealkyl)2, -N(C3-ecycloalkyl)2, -S(=O)oCi. ealkyl, -S(=O)oC3-ecycloalkyl, and CN;R3is selected from the group consisting of:(a) hydrogen,(b) halogen,(c) CN,(d) CF3,(e) -Ci-ealkyl,(f) -Ci-6alkyl-C(=O)OH,(g) -O-(R7),(h) -S(=O)oR7,(1) -N(R7)(R8),(j) -N(R7)-C(=O)-(R8),(k) -N(R7)-C(=O)-O-(R8),(l) -N(R7)S(=O)2(R8),(m) -Cs-ecycloalkyl,(n) -C(=O)(R7),(o) aryl,(p) heteroaryl,(q) -OC(=O)N(R7)(R8),(r) -S(=O)2N(R7)(R8),(s) -C(=O)N(R7)(R8),(t) -C(R7)(R8)OH,(u) -NHC(=O)-N(R7)(R8),(v) -Cs-ecycloalkyl-COOH,(w) heterocycle, andWSGR Docket No. 53238-724.601(x) -Ci.6alkylC(=O)-N(R7)(R8),wherein the alkyl portion of choices (e), (f) and (x), and the cycloalkyl portion of choices (m) and (v) are optionally substituted with halogen or hydroxyl, andwherein the aryl of choice (o), the heteroaryl of choice (p), and the heterocycle of choice (w) are optionally mono- or di-substituted with substituents selected from halogen, nitro, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, -NH(Ci-6alkyl), -NH(C3-6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, hydroxyl and CN;R4and R4are each independently selected from the group consisting of:(a) hydrogen,(b) -N(R7)(R8),(c) -N(R7)S(=O)2R8,(d) -N(R7)-C(=O)R8,(e) -N(R7)C(=O)OR8,(f) -S(=O)oR7,(g) -S(=O)2N(R7)(R8),(h) -C(=O)R7,(i) -C(=O)N(R7)(R8),(j) -OC(=O)N(R7)(R8),(k) -O-R7,(l) -C(R7)(R8)OH,(m) -C1-4alkyl-C(=O)NHS(=O)2R7,(n) -C1-4alkyl-S(=O)2NHC(=O)R7,(o) -C1-4alkyl-C(=O)-N(R7)(R8),(p) -C1-4alkyl-N(R7)C(=O)(R8),(q) -C1-4alkyl-N(R7)S(=O)2(R8),(r) -C1-4alkyl-S(=O)2N(R7)(R8),(s) -Ci.4alkyl-N(R7)C(=O)O(R8)(t) -Ci.4alkyl-O-C(=O)N(R7)(R8)(u) -Ci.4alkyl-C(=O)(R7),(v) -C1-4alkyl-C(R7)(R8)OH,(w) -C1-4alkyl-O(R7),(x) -C1-6alkyl-C(=O)OH,(y) -C26alkenyl-C(=O)OH,(z) -C3-6cycloalkyl-C(=O)OH,(aa) -C3-6cycloalkyl-C(=O)NHS(=O)2R7,(bb) -C3-6cycloalkyl-S(=O)2NHC(=O)R7,(cc) -C3-6cycloalkyl-C(=O)-N(R7)(R8),WSGR Docket No. 53238-724.601(dd) -C3-6cycloalkyl-N(R7)C(=O)(R8),(ee) -C3-6cycloalkyl-N(R7)S(=O)2(R8),(ff) -C3-6cycloalkyl-S(=O)2N(R7)(R8),(gg) -C3-6cycloalkyl-N(R7)C(=O)O(R8),(hh) -C3-6cycloalkyl-O-C(=O)N(R7)(R8),(ii) -C3-6cycloalkyl-C(=O)(R7),(jj) -C3.6cycloalkyl-C(R7)(R8)OH,(kk) -C3-6cycloalkyl-O(R7),(11) -C(=O)OH,(mm) aryl,(rm) heteroaryl,(oo) -C(=O)N(R7)S(=O)2(R8),(pp) -S(=O)2N(R7)C(=O)(R8),(qq) -NHS(=O)2N(R7)(R8),(rr) -NHC(=O)N(R7)(R8),(ss) -CH(OH)-C(=O)-N(R7)(R8),(tt) -C(=O)-C(=O)-N(R7)(R8),(uu) -C3.6cycloalkyl,(vv) -CF3,(ww) -Ci.6alkyl N(R7)(R8),(xx) -heterocycle,(yy) -Ci-ealkyl,(zz) halogen, and(aaa) -O-Ci.6alkyl-N(R7)(R8),wherein the alkyl portion of choices (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (ww), (yy) and (aaa), the alkenyl portion of choice (y), and the cycloalkyl portion of choices (z), (aa), (bb), (cc), (dd), (ee), (ff), (gg), (hh), (ii), (jj), (kk) and (uu), are optionally mono- or di-substituted with halogen, CN, aryl, Ci-ealkyl, halo Ci-ealkyl, C3.6cycloalkyl, Ci-ealkoxy, or C3.6cycloalkoxy, andwherein the aryl of choice (mm), the heteroaryl of choice (nn), and the heterocycle of choice (xx) are optionally mono- or di-substituted with substituents selected from halogen, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, C3.6cycloalkyl, C3.6cycloalkoxy, -NH(Ci-6alkyl), -NH(C3.6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oCi-6alkyl, -S(=O)oC3.6cycloalkyl, hydroxyl and CN, orwherein R3and R4or R4and R4are joined together to form a 5 - or 6-membered heterocyclic ring, said ring having one heteroatom selected from O and N, wherein said ring is optionally substituted with -C(=O)OH, or -Ci-6alkyl-C(=O)OH, with the proviso that at least one of R3, R4and R4is other than hydrogen;R5is selected from the group consisting of:WSGR Docket No. 53238-724.601(a) hydrogen,(b) -C1-6alkyl,(c) -C1-4alkyl(R7),(d) aryl,(e) heteroaryl,(f) -Cs-ecycloalkyl,(g) -C3-6cycloalkyl(R7),(h) -C3-6cycloalkyl-O(R7),(i) -Ci^alkyl-Cs-ecycloalkyl,(j) -Ci ^alkoxy, and(k) -C,, cycloalkoxy.wherein the alkyl portion of choices (b), (c), (i) and (j ), the cycloalkyl portion of choices (f), (g), (h), (i) and (k) are optionally substituted with halogen or C1-4alkyl, andwherein the aryl of choice (d) and the heteroaryl of choice (e), are optionally mono- or di-substituted with substituents selected from halogen, nitro, Ci-ealkyl, CF,. Ci-ealkoxy, halo Ci-ealkyl, aryl, heteroaryl, Ckecycloalkyl. Cs-ecycloalkoxy, and CN;R6is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,(c) -Ci-ealkylaryl,(d) -Ci -ealkylheteroaryl,(e) -S(=O)oCi-6alkyl(R7),(f) -C(=O)Ci-6alkyl(R7),(g) -C3-6cycloalkyl,(h) aryl,(i) hetereoaryl,(j) -C(=O)C3-6cycloalkyl(R7),(k) -S(=O)oC3-6cycloalkyl(R7), and(l) -C1-6alkyl(R7),wherein the alkyl portion of choices (b), (c), (d), (e), (f), and (1) and the cycloalkyl portion of choices (g), (j), and (k), are optionally substituted with halogen or C1-4alkyl, andwherein the aryl portion of choices (c) and (h), and the heteroaryl portion of choices (d) and (i), are optionally mono- or di-substituted with substituents selected from halogen, nitro, -CF3, Ci-ealkyl, Ci-6alkoxy, halo Ci-galkyl, C;.,, cycloalkyl. C’3.,, cycloalkoxy. aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH(Ci-6alkyl), -NH(C3-ecycloalkyl), -N(Ci-6alkyl)2, -N(C3-ecycloalkyl)2, -S(=O)oCi-6alkyl, S(=O)oC3-6cycloalkyl, and CN;R7and R8are each independently selected from the following:WSGR Docket No. 53238-724.601(a) hydrogen,(b) -Chalky!,(c) -Cs-ecycloalkyl,(d) -aryl,(e) -heteroaryl,(f) -Ci-ealkylaryl,(g) -Ci -ealkylheteroaryl,(h) -C(=O)Ci-6alkyl,(i) -S(=O)o-aryl,(j) -Ci-ealkyl-C’s-ecycloalkyl. and(k) CF3,wherein the alkyl of choices (b), (f), (g), (h), and (j), and the cycloalkyl of choices (c) and (j), are each optionally mono-, di- or tri-substituted with halogen, andwherein the aryl portion of choices (d), (f) and (i), and the heteroaryl portion of choices (e) and (g), are each optionally mono- or di-substituted with substituents selected from halogen, -C(=O)OH, -CF3, -NHC(=0)CH3, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, Cs-ecycloalkyl, Ck,, cycloalkoxy. -NH(Ci-salkyl), -NH(C3-6cycloalkyl), -N(Ci-3alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oCi-4alkyl, S(=O)oC3-ecycloalkyl, aryl, heteroaryl, hydroxyl, and CN;R9and R10are each independently selected from the following(a) hydrogen,(b) -C1-6alkyl,(c) -C3-6cycloalkyl,(d) halogen,(e) -OC3-6cycloalkyl,(f) CF3, and(g) -Ci-6alkoxy,wherein the alkyl portion of choice (b) and the cycloalkyl portion of choices (c) and (e), are each optionally mono-, di- or tri- substituted with halogen. In the alternative, choice (g) of R9and R10may also be mono-, di- or tri-substituted with halogen.

[0009] Within this aspect there is a genus wherein: X is selected from the group consisting of -(CH2)m-, and -(CH2)m-O-(CH2)n-, optionally mono- or di-substituted with halogen, where m + n is 2, 3 or 4.

[0010] Within this genus there is a sub-genus wherein: X is selected from -CH2CH2CH2-, or -CF2CH2CH2-.

[0011] Within this aspect there is an alternative genus wherein: X is selected from the group consisting of -(CH2)m-, and -(CH2)m-O-(CH2)n-, optionally mono- or di-substituted with halogen, where m + n is 1, 2, 3 or 4.WSGR Docket No. 53238-724.601

[0012] Within this alternative genus there is a sub-genus wherein: X is selected from -CH2CH2CH2-, -CF2CH2CH2-, or -OCH2-.

[0013] Within this aspect there is a genus wherein: Al is a substituted phenyl or substituted pyridine.

[0014] Within this genus there is a sub-genus wherein: A2 is A2a.

[0015] Within this sub-genus there is a class wherein: A2a is a substituted phenyl, substituted pyrimidine, substituted pyrazine, or substituted pyridine.

[0016] Within this aspect these is a genus wherein: Y is O.

[0017] Within this aspect there is a genus wherein:R1and R2are each independently selected from the group consisting of:(a) hydrogen,(b) halogen,(c) CN,(d) CF3,(e) -Ci.ealkyl,(f) -O-(R7),(g) -C3-6cycloalkyl, and(h) -N(R7)(R8),wherein the alkyl portion of choice (e) and the cycloalkyl portion of choice (g) are optionally substituted with halogen.

[0018] Within this genus there is a sub-genus wherein:R1and R2are each independently selected from:(a) hydrogen,(b) halogen,(c) CF3,(d) -Cnealkyl, and(e) -O-(R7),wherein the alkyl portion of choice (d) is optionally substituted with halogen.

[0019] Within this sub-genus there is a class wherein R1and R2are each hydrogen.

[0020] Within this aspect there is a genus wherein:R3is selected from the group consisting of:(a) hydrogen,(b) halogen,(c) CF3,(d) -Cuealkyl,(e) -O-(R7),(f) -S(=O)oR7,(g) -Cs-. cycloalkyl.WSGR Docket No. 53238-724.601(h) aryl,(i) heteroaryl,(j) -S(=O)2N(R7)(R8),(k) -C(R7)(R8)OH,(l) heterocycle, and(m) -N(R7)S(=O)2(R8),wherein the alkyl portion of choice (d) and the cycloalkyl portion of choice (g) are optionally substituted with halogen or hydroxyl, andwherein the aryl of choice (h), the heteroaryl of choice (i), and the heterocycle of choice (1) are optionally mono- or di-substituted with substituents selected from halogen, nitro, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, -NH(Ci-6alkyl), -NH(C3-6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, hydroxyl and CN.

[0021] Within this genus there is a sub-genus wherein:R3is selected from the group consisting of:(a) hydrogen,(b) -O-(R7),(c) -N(R7)S(=O)2(R8), and(d) -Ci-ealkyl,wherein the alkyl portion of choice (d) is optionally substituted with halogen or hydroxyl.

[0022] Within this aspect there is a genus wherein:R4and R4are each independently selected from the group consisting of:(a) hydrogen,(b) -N(R7)S(=O)2R8,(c) -N(R7)-C(=O)R8,(d) -S(=O)oR7,(e) -S(=O)2N(R7)(R8),(f) -C(=O)N(R7)(R8),(g) -O-(R7),(h) -C(R7)(R8)OH,(i) -Ci.4alkyl-C(=O)NHS(=O)2R7,(j) -Ci.4alkyl-S(=O)2NHC(=O)R7,(k) -C1-4alkyl-C(=O)-N(R7)(R8),(l) -C1-4alkyl-N(R7)C(=O)(R8),(m) -Ci.4alkyl-N(R7)S(=O)2(R8),(n) -C1-4alkyl-S(=O)2N(R7)(R8),(o) -C1-4alkyl-C(R7)(R8)OH,(p) -Ci-4alkyl-O(R7),WSGR Docket No. 53238-724.601(q) -C1-6alkyl-C(=O)OH,(r) -C26alkenyl-C(=O)OH,(s) -C3-6cycloalkyl-C(=O)OH,(t) -C3-6cycloalkyl-C(=O)NHS(=O)2R7,(u) -C3-6cycloalkyl-S(=O)2NHC(=O)R7,(v) -C3-6cycloalkyl-C(=O)-N(R7)(R8),(w) -C3-6cycloalkyl-N(R7)S(=O)2(R8),(x) -C3-6cycloalkyl-S(=O)2N(R7)(R8),(y) -C3-6cycloalkyl-N(R7)C(=O)O(R8),(z) -C3.6cycloalkyl-C(R7)(R8)OH,(aa) -C3.6cycloalkyl-O(R7),(bb) -C(=O)OH,(cc) aryl,(dd) heteroaryl,(ee) -C(=O)N(R7)S(=O)2(R8),(ff) -S(=O)2N(R7)C(=O)(R8),(gg) -NHS(=O)2N(R7)(R8),(hh) -NHC(=O)N(R7)(R8),(ii) -C3-6cycloalkyl,(jj) CF3,(kk) heterocycle,(ll) -C1-6alkyl, and(mm) halogen,wherein the alkyl portion of choices (i), (j), (k), (1), (m), (n), (o), (p), (q), and (11), the alkenyl portion of choice (r), and the cycloalkyl portion of choices (s), (t), (u), (v), (w), (x), (y), (z), and (aa) are optionally mono- or di-substituted with halogen, CN, aryl, Ci-ealkyl, halo Ci-ealkyl, C3.6cycloalkyl, Ci-ealkoxy, or C3.6cycloalkoxy and,wherein the aryl of choice (cc), the heteroaryl of choice (dd), and the heterocycle of choice (kk) are optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, C3.6cycloalkyl, C3.6cycloalkoxy, -NH(Ci -ealkyl), -NH(C3.ecycloalkyl), -N(Ci-ealkyl)2, -N(C3.ecycloalkyl)2, -S(=O)oCi-ealkyl, -S(=O)oC3.6cycloalkyl, and CN. In the alternative, choice (ii) of R4and R4may also be mono- or di-substituted with halogen, CN, aryl, Ci-ealkyl, halo Ci-ealkyl, C3.ecycloalkyl, Ci-ealkoxy, or C3-ecycloalkoxy halogen.

[0023] Within this genus there is a sub-genus wherein:R4and R4are each independently selected from the group consisting of:(a) hydrogen,(b) -N(R7)S(=O)2R8,WSGR Docket No. 53238-724.601(c) -N(R7)-C(=O)R8,(d) -0-(R7),(e) -C(R7)(R8)OH,(f) -C1-4alkyl-S(=O)2NHC(=O)R7,(g) -C1-4alkyl-N(R7)S(=O)2(R8),(h) -C1-4alkyl-S(=O)2N(R7)(R8),(i) -C1-4alkyl-O(R7),(j) -Ci.6alkyl-C(=0)0H,(k) -C3-6cycloalkyl-C(=O)OH,(l) -C3-6cycloalkyl-N(R7)S(=O)2(R8),(m) -C3-6cycloalkyl-S(=O)2N(R7)(R8),(n) -C3-6cycloalkyl-O(R7),(o) -C(=O)OH,(p) -C(=O)N(R7)S(=O)2(R8),(q) -S(=O)2N(R7)C(=O)(R8),(r) -NHS(=O)2N(R7)(R8),(s) -C3.6cycloalkyl,(t) CF3,(u) heterocycle,(v) -C1-6alkyl, and(w) halogen,wherein the alkyl portion of choices (f), (g), (h), (i), (j), and (v), and the cycloalkyl portion of choices (k), (1), (m), (n), and (s), are optionally mono- or di-substituted with halogen, CN, aryl, Ci-ealkyl, halo Ci-ealkyl, C3-ecycloalkyl, Ci-ealkoxy, or C3-ecycloalkoxy, andwherein the heterocycle of choice (u) is optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, C3-ecycloalkyl, C3-ecycloalkoxy, -NH(Ci -ealkyl), -NH(C3.ecycloalkyl), -N(Ci-ealkyl)2, -N(C3.ecycloalkyl)2, -S(=O)oCi. ealkyl, -S(=O)oC3. ecycloalkyl and CN.

[0024] Within this sub-genus there is class wherein:R4and R4are each independently selected from the group consisting of:(a) -C(R7)(R8)OH,(b) -N(R7)S(=O)2R8,(c) -O-(R7),(d) -Ci-6alkyl-C(=O)OH,(e) -C(=O)OH,(f) -NHS(=O)2N(R7)(R8),(g) -C3-ecycloalkyl,WSGR Docket No. 53238-724.601(h) CF3,(i) heterocycle,(j) -C1-6alkyl, and(k) halogen,wherein the alkyl portion of choices (d) and (j), and the cycloalkyl portion of choice (g) are optionally mono- or di-substituted with halogen, CN, aryl, C1-6alkyl, halo C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy, or C3-6cycloalkoxy, andwherein the heterocycle of choice (i) is optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, C. cycloalkyl. C,, cycloalkoxy. -NH(Ci-6alkyl), -NH(C3-6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oCi-6alkyl, -S(=O)oC3-ecycloalkyl, and CN.

[0025] Within this aspect there is a genus wherein:R5is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,(c) -C1-4alkyl(R7),(d) aryl,(e) heteroaryl,(f) -C3-6cycloalkyl, and(g) -Ci-4alkyl-C3-6cycloalkyl,wherein the alkyl portion of choices (b), (c), and (g), the cycloalkyl portion of choices (f) and (g), are optionally substituted with halogen or C1-4alkyl, andwherein the aryl of choice (d) and the heteroaryl of choice (e), is optionally mono- or di-substituted with substituents selected from halogen, nitro, Ci-ealkyl, CF3, Ci-ealkoxy, halo Ci-ealkyl, aryl, heteroaryl, Ck. cycloalkyl. Ck. cycloalkoxy. and CN.

[0026] Within this genus there is a sub-genus whereinR5is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl, and(c) -C1-4alkyl(R7),wherein the alkyl portion of choices (b) and (c) is optionally substituted with halogen or Ci.4alkyl.

[0027] Within this aspect there is a genus wherein:R6is selected from the group consisting of:(a) -C1-6alkylaryl,(b) -Ci-6alkylheteroaryl,(c) -Ck.cycloalkyl.(d) aryl,WSGR Docket No. 53238-724.601(e) heteroaryl, and(f) -C1-6alkyl(R7),wherein the alkyl portion of choices (a), (b) and (f), and the cycloalkyl portion of choice (c) are optionally substituted with halogen or C1-4alkyl, andwherein the aryl portion of choices (a) and (d), and the heteroaryl portion of choices (b) and (e), are optionally mono- or di-substituted with substituents selected from halogen, nitro, CF3, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, Ck.cycloalkyl. Ck,, cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH(Ci-6alkyl), -NH(C3-6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, and CN.

[0028] Within this genus there is a sub-genus wherein:R6is selected from the group consisting of:(a) -C1-6alkylaryl,(b) -Ci-6alkylheteroaryl, and(c) -Ci.6alkyl(R7),wherein the alkyl portion of choices (a), (b), and (c) is optionally substituted with halogen or C1-4alkyl, andwherein the aryl portion of choice (a), and the heteroaryl portion of choice (b), are optionally mono- or di-substituted with substituents selected from halogen, nitro, CF3, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -N(C1-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, and CN.

[0029] Within this aspect there is a genus wherein:R7and R8are each independently selected from the following:(a) hydrogen,(b) -C1-6alkyl,(c) -Ci-.cycloalkyl.(d) aryl,(e) heteroaryl, and(f) CF3,wherein the alkyl of choice (b) and the cycloalkyl of choice (c) are optionally mono-, di- or trisubstituted with halogen, andwherein the aryl of choice (d) and the heteroaryl of choice (e) are optionally mono- or di-substituted with substituents selected from halogen, -C(=O)OH, CF3, -NHC(=O)-CH3, nitro, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, Ck.cycloalkyl. C’3.,, cycloalkoxy. -NH(Ci.3alkyl), -NH(C3-6cycloalkyl), -N(Ci.3alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oCi-4alkyl, -S(=O)oC3-6cycloalkyl, aryl, heteroaryl, hydroxyl, and CN.

[0030] Within this aspect there is a genus wherein:R9and R10are each independentlyWSGR Docket No. 53238-724.601(a) hydrogen,(b) -C1-6alkyl,(c) halogen,(d) CF3, and(e) -C1-6alkoxy,wherein the alkyl of choice (b) is optionally mono-, di- or tri-substituted with halogen. In the alternative, the alkyl portion of choice (e) of R9and R10may also be mono-, di- or tri-substituted with halogen.

[0031] Within this aspect there is a genus wherein:X is selected from the group consisting of -(CH2)m-, and -(CH2)m-O-(CH2)n-, optionally mono or disubstituted with halogen, where m + n is 2, 3 or 4;Y is O;Al is a substituted phenyl or substituted pyridine;A2 is A2a;R1and R2are each independently selected from the group consisting of:(a) hydrogen,(b) halogen,(c) CN,(d) CF3,(e) -C1-6alkyl,(f) -O-(R7),(g) -C3-6cycloalkyl, and(h) -N(R7)(R8),wherein the alkyl portion of choice (e) and the cycloalkyl portion of choice (g) are optionally substituted with halogen;R3is selected from the group consisting of:(a) hydrogen,(b) halogen,(c) CF3,(d) -C1-6alkyl,(e) -O-(R7),(f) -S(=O)oR7,(g) -C3-6cycloalkyl,(h) aryl,(i) heteroaryl,(j) -S(=O)2N(R7)(R8),(k) -C(R7)(R8)OH,WSGR Docket No. 53238-724.601(l) heterocycle, and(m) -N(R7)S(=O)2(R8),wherein the alkyl portion of choice (d) and the cycloalkyl portion of choice (g) are optionally substituted with halogen or hydroxyl, andwherein the aryl of choice (h), the heteroaryl of choice (i), and the heterocycle of choice (1) are optionally mono- or di-substituted with substituents selected from halogen, nitro, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, -NH(Ci-6alkyl), -NH(C3-6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, hydroxyl and CN;R4and R4are each independently selected from the group consisting of:(a) hydrogen,(b) -N(R7)S(=O)2R8,(c) -N(R7)-C(=O)R8,(d) -S(=O)oR7,(e) -S(=O)2N(R7)(R8),(f) -C(=O)N(R7)(R8),(g) -O-(R7),(h) -C(R7)(R8)OH,(i) -C1-4alkyl-C(=O)NHS(=O)2R7,(j) -C1-4alkyl-S(=O)2NHC(=O)R7,(k) -C1-4alkyl-C(=O)-N(R7)(R8),(l) -C1-4alkyl-N(R7)C(=O)(R8),(m) -C1-4alkyl-N(R7)S(=O)2(R8),(n) -C1-4alkyl-S(=O)2N(R7)(R8),(o) -C1-4alkyl-C(R7)(R8)OH,(p) -C1-4alkyl-O(R7),(q) -C1-6alkyl-C(=O)OH,(r) -C2-6alkenyl-C(=O)OH,(s) -C3-6cycloalkyl-C(=O)OH,(t) -C3-6cycloalkyl-C(=O)NHS(=O)2R7,(u) -C3-6cycloalkyl-S(=O)2NHC(=O)R7,(v) -C3-6cycloalkyl-C(=O)-N(R7)(R8),(w) -C3-6cycloalkyl-N(R7)S(=O)2(R8),(x) -C3-6cycloalkyl-S(=O)2N(R7)(R8),(y) -C3-6cycloalkyl-N(R7)C(=O)O(R8),(z) -C3-6cycloalkyl-C(R7)(R8)OH,(aa) -C3-6cycloalkyl-O(R7),(bb) -C(=O)OH,WSGR Docket No. 53238-724.601(cc) aryl,(dd) heteroaryl,(ee) -C(=O)N(R7)S(=O)2(R8),(ff) -S(=O)2N(R7)C(=O)(R8),(gg) -NHS(=O)2N(R7)(R8),(hh) -NHC(=O)N(R7)(R8),(ii) -C3-6cycloalkyl,(jj) CF3,(kk) heterocycle,(ll) -C1-6alkyl, and(mm) halogen,wherein the alkyl portion of choices (i), (j), (k), (l), (m), (n), (o), (p), (q), and (ll), the alkenyl portion of choice (r), and the cycloalkyl portion of choices (s), (t), (u), (v), (w), (x), (y), (z), and (aa) are optionally mono- or di-substituted with halogen, CN, aryl, C1-6alkyl, halo C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy, or C3-6cycloalkoxy and,wherein the aryl of choice (cc), the heteroaryl of choice (dd), and the heterocycle of choice (kk) are optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -N(C1-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, and CN;R5is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,(c) -C1-4alkyl(R7),(d) aryl,(e) heteroaryl,(f) -C3-6cycloalkyl, and(g) -C1-4alkyl-C3-6cycloalkyl,wherein the alkyl portion of choices (b), (c) and (g), the cycloalkyl portion of choices (f) and (g), are optionally substituted with halogen or C1-4alkyl, andwherein the aryl of choice (d) and the heteroaryl of choice (e), are optionally mono- or di-substituted with substituents selected from halogen, nitro, C1-6alkyl, CF3, C1-6alkoxy, halo C1-6alkyl, aryl, heteroaryl, C3-6cycloalkyl, C3-6cycloalkoxy, and CN;R6is selected from the group consisting of:(a) -C1-6alkylaryl,(b) -Ci-6alkylheteroaryl,(c) C3-6cycloalkyl,(d) aryl,WSGR Docket No. 53238-724.601(e) heteroaryl, and(f) -C1-6alkyl(R7),wherein the alkyl portion of choices (a), (b) and (f), and the cycloalkyl portion of choice (c) are optionally substituted with halogen or C1-4alkyl, andwherein the aryl portion of choices (a) and (d), and the heteroaryl portion of choices (b) and (e), are optionally mono- or di-substituted with substituents selected from halogen, nitro, CF3, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, C.cycloalkyl. Ck,, cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH(Ci-6alkyl), -NH(C3-6cycloalkyl), -N(Ci-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, and CN;R7and R8are each independently selected from the following:(a) hydrogen,(b) C1-6alkyl,(c) C3-6cycloalkyl,(d) aryl,(e) heteroaryl, and(f) CF3,wherein the alkyl of choice (b) and the cycloalkyl of choice (c) are optionally mono-, di- or trisubstituted with halo, andwherein the aryl of choice (d) and the heteroaryl of choice (e) are optionally mono- or di-substituted with substituents selected from halogen, -C(=O)OH, CF3, -NHC(=0)-CH3, nitro, Ci-ealkyl, Ci-ealkoxy, haloCi. ealkyl, Ck.cycloalkyl. Ck.cycloalkoxy. -NH(Ci-3alkyl), -NH(C3-ecycloalkyl), -N(Ci-3alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oCi-4alkyl, -S(=O)oC3-6cycloalkyl, aryl, heteroaryl, hydroxyl, and CN; andR9and R10are each independently(a) hydrogen,(b) -C1-6alkyl,(c) halogen,(d) CF3, and(e) C1-6alkoxy,wherein the alkyl of choice (b) is optionally mono-, di- or tri-substituted with halogen. In the alternative aspect, choice (ii) of R4and R4'may also be mono- or di-substituted with halogen, CN, aryl, C1-6alkyl, halo C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy, or C3-6cycloalkoxy halogen; and the alkyl portion of choice (e) is optionally mono-, di- or tri-substituted with halogen and choice (e) of R9and R10may also be mono-, di- or tri-substituted with halogen

[0032] Within this genus there is a sub-genus wherein:A2 is A2a, and A2a is a substituted phenyl, substituted pyrimidine, substituted pyrazine, or substituted pyridine;WSGR Docket No. 53238-724.601R1and R2are each independently selected from:(a) hydrogen,(b) halogen,(c) CF3,(d) C1-6alkyl, and(e) -O-(R7),wherein the alkyl portion of choice (d) is optionally substituted with halogen;R3is selected from the group consisting of:(a) hydrogen,(b) -O-(R7),(c) -N(R7)S(=O)2(R8), and(d) -C1-6alkyl,wherein the alkyl portion of choice (d) is optionally substituted with halogen or hydroxyl; R4and R4are each independently selected from the group consisting of:(a) hydrogen,(b) -N(R7)S(=O)2R8,(c) -N(R7)-C(=O)R8,(d) -O-(R7),(e) -C(R7)(R8)OH,(f) -C1-4alkyl-S(=O)2NHC(=O)R7,(g) -C1-4alkyl-N(R7)S(=O)2(R8),(h) -C1-4alkyl-S(=O)2N(R7)(R8),(i) -C1-4alkyl-O(R7),(j) -C1-6alkyl-C(=O)OH,(k) -C3-6cycloalkyl-C(=O)OH,(l) -C3-6cycloalkyl-N(R7)S(=O)2(R8),(m) -C3-6cycloalkyl-S(=O)2N(R7)(R8),(n) -C3-6cycloalkyl-O(R7),(o) -C(=O)OH,(p) -C(=O)N(R7)S(=O)2(R8),(q) -S(=O)2N(R7)C(=O)(R8),(r) -NHS(=O)2N(R7)(R8),(s) -C3.6cycloalkyl,(t) CF3,(u) heterocycle,(v) -C1-6alkyl, and(w) halogen,WSGR Docket No. 53238-724.601wherein the alkyl portion of choices (f), (g), (h), (i), (j), and (v), and the cycloalkyl portion of choices (k), (1), (m), (n), and (s), are optionally mono- or di-substituted with halogen, CN, aryl, C1-6alkyl, halo C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy, or C3-6cycloalkoxy, andwherein the heterocycle of choice (u) is optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -N(C1-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl and CN;R5is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl, and(c) -C1-4alkyl(R7),wherein the alkyl portion of choices (b) and (c) is optionally substituted with halogen or Ci-4alkyl; R6is selected from the group consisting of:(a) -C1-6alkylaryl,(b) -C1-6alkylheteroaryl, and(c) -C1-6alkyl(R7),wherein the alkyl portion of choices (a), (b), and (c) is optionally substituted with halogen or C1-4alkyl, andwherein the aryl portion of choice (a), and the heteroaryl portion of choice (b), are optionally mono- or di-substituted with substituents selected from halogen, nitro, CF3, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -N(C1-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, and CN.

[0033] Within this sub-genus there is a class wherein:R4and R4are each independently selected from the group consisting of:(a) -C(R7)(R8)OH,(b) -N(R7)S(=O)2R8,(c) -O-(R7),(d) -C1-6alkyl-C(=O)OH,(e) -C(=O)OH,(f) -NHS(=O)2N(R7)(R8),(g) C3-6cycloalkyl,(h) CF3,(i) heterocycle,(j) -C1-6alkyl, and(k) halogen,WSGR Docket No. 53238-724.601wherein the alkyl portion of choices (d) and (j), and the cycloalkyl portion of choice (g) are optionally mono- or di-substituted with halo, CN, aryl, Ci-ealkyl, halo Ci-ealkyl, Cs-ecycloalkyl, Ci-ealkoxy, or C3-ecycloalkoxy, andwherein the heterocycle of choice (i) is optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, C1-6alkyl, C1-6alkoxy, halo C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -N(C1-6alkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oC1-6alkyl, -S(=O)oC3-6cycloalkyl, and CN.

[0034] Within this class there is a sub-class wherein of Formula laor a pharmaceutically acceptable salt thereof.

[0035] Within this sub-class there is a sub-sub-class wherein of Formula lbor a pharmaceutically acceptable salt thereof.

[0036] In some embodiments, R3is not hydrogen. In some embodiments, R4is not hydrogen. In some embodiments, R3is not hydrogen; and R4is not hydrogen.

[0037] In one aspect, described herein are the following compounds:2-(3'-(3-( l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[ 1, 1'-biphenyl]-3-yl)acetic acid,2-(3'-(3-( l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[ 1, 1'-biphenyl]-4-yl)acetic acid,3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[ 1,1'-biphenyl] -3 -carboxylic acid,3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[ 1,1'-biphenyl]-4-carboxylic acid,l-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1 '-biphenyl] -3 -yl)cyclopropanecarboxylic acid,WSGR Docket No. 53238-724.6012-(3'-(3-( l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1 '-biphenyl] -3 -yl)acetic acid,l-(3'-(3-( l-(4-( / -biityl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-IH-l.2.4-triazol-3-yl)propyl)-| 1.1'-biphenyl] -3 -yl)cyclopropanecarboxylic acid,1-(3'-(3-( l-(4-( / -biityl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-| 1.1'-biphenyl] -4-yl)cyclopropanecarboxylic acid,3'-(3-( l-(4-( / c77-butyl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-4-mcthoxy- [1,1 '-biphenyl] -3 -carboxylic acid,3'-(3-( l-(4-( / c77-butyl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-4-cthoxy- [1,1 '-biphenyl] -3 -carboxylic acid,2-(3'-(3-(l-(4-( / c77-biityl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-4-propoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid,N-(6-(3-(3-( l-(4-(Yert-butyl)benzyl)-4-ethyl-5 -oxo-4, 5 -dihydro- 1H- 1,2, 4-triazol-3-yl)propyl)phenyl)pyridin-3-yl)benzenesulfonamide,2-(3'-(3-(l-(4-( / c77-biityl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-4-methoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid,1-(3'-(3-( l-(4-( / c77-butyl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-4-mcthyl- [1,1 '-biphenyl] -3 -yl)cyclopropanecarboxylic acid,2-(4-(benzyloxy)-3'-(3-( 1 -(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4, 5 -dihydro- 1H- 1,2, 4-triazol-3-yl)propyl)-[ 1, 1 '-biphenyl] -3-yl)acetic acid,2-(3'-(3-(l-(4-( / c77-biityl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)-4- (cyclopropylmethoxy) -[ 1, 1 '-biphenyl] -3-yl)acetic acid,2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-fluoro- [1,1 '-biphenyl] -3 -yl)acetic acid,2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-6-ethoxy- [1,1 '-biphenyl] -3 -yl)acetic acid,3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-propoxy- [1,1 '-biphenyl] -3 -carboxylic acid,N-((3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[ 1,1'-biphenyl]-3-yl)methyl)benzenesulfonamide,3-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-methoxy-[1,1 '-biphenyl] -3 -yl)propanoic acid,2-(3'-(3-( l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)-l, 1-difluoropropyl)-4-ethoxy-[ 1, 1 '-biphenyl] -3-yl)acetic acid,N-(6-(3-(3-( l-(4-(tert-butyl)benzyl)-4-ethyl-5 -oxo-4, 5 -dihydro- 1H-1, 2, 4-triazol-3-yl)-l, 1-difluoropropyl)phenyl)pyridin-3-yl)benzenesulfonamide,WSGR Docket No. 53238-724.6012-(5-(6-(3-(l-(4-( / c77-biityl)bcnzyl)-4-cthyl-5-oxo-4.5-dihydro-l / / -l.2.4-triazol-3-yl)propyl)pyridin-2-yl)-2-methoxyphenyl)acetic acid,3-(3-(3'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-3-yl)propyl)-1-(4-(tert-butyl)benzyl)-4-ethyl-1H-1,2,4-triazol-5(4H)-one,2-(5-(4-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)pyrimidin-2-yl)-2-ethoxyphenyl)acetic acid,2-(5-(6-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)pyrimidin-4-yl)-2-ethoxyphenyl)acetic acid,(3'-(3-(l-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-3-methoxy-[1,1 '-biphenyl] -4-yl)acetic acid,(3 '-(3 -( 1 -(4-(tert-Butyl)benzyl)-4-ethyl-5 -oxo-4, 5 -dihydro- 1H- 1,2,4-triazol-3 -yl)propyl)-3 -ethoxy-[1,1 '-biphenyl] -4-yl)acetic acid,(3'-(3-(l-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-3-propoxy-[1,1 '-biphenyl] -4-yl)acetic acid,2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-3-hydroxy-[1,1 '-biphenyl] -4-yl)acetic acid,2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-isopropoxy-[l, l'-biphenyl]-3-yl)acetic acid,2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)-[ 1, 1 '-biphenyl] -3-yl)acetic acid,or a pharmaceutically acceptable salt thereof.

[0038] In another aspect the disclosure is directed to a pharmaceutical composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In another aspect the disclosure is directed to a method of treating a cancer which is negatively impacted by diminution in its metabolism of fatty acid, through the administration of a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof. Within this aspect there is a genus wherein the cancer is selected from prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, and melanoma. In another aspect the disclosure is directed to a method of treating cancer involving the administration of a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof. In another aspect the disclosure is directed to a method of preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers through the administration of a therapeutically effective amount of a compound according to Claim 1, or a pharmaceutically acceptable salt thereof.DEFINITIONS

[0039] The term "patient" includes mammals such as mice, rats, cows, sheep, pigs, rabbits, goats, horses, monkeys, dogs, cats, and humans.WSGR Docket No. 53238-724.601

[0040] The term "halo" or "halogen" refers to any radical of fluorine, chlorine, bromine or iodine.

[0041] The term "alkyl" refers to a saturated hydrocarbon chain that may be a straight chain or branched chain, containing the indicated number of carbon atoms. For example, Ci-ealkyl indicates that the group may have from 1 to 6 (inclusive) carbon atoms in it. Any atom can be optionally substituted, e.g., by one or more substituents. Examples of alkyl groups include without limitation methyl, ethyl, n-propyl, isopropyl, w-butyl, scc-butyl and tert-butyl.

[0042] The term "haloalkyl" refers to an alkyl group, in which at least one hydrogen atom is replaced by halo. In some embodiments, more than one hydrogen atom (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) are replaced by halo. In these embodiments, the hydrogen atoms can each be replaced by the same halogen (e.g., fluoro) or the hydrogen atoms can be replaced by a combination of different halogens (e.g., fluoro and chloro). " Haloalkyl" also includes alkyl moieties in which all hydrogens have been replaced by halo (sometimes referred to herein as perhaloalkyl, e.g., perfluoroalkyl, such as trifluoromethyl). Any atom can be optionally substituted, e.g., by one or more substituents.

[0043] As referred to herein, the term "alkoxy" refers to a group of formula -O(alkyl). Alkoxy can be, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, iso-butoxy, sec-butoxy, pentoxy, 2-pentoxy, 3-pentoxy, or hexyloxy. Likewise, the term "thioalkoxy" refers to a group of formula -S(alkyl). The terms "haloalkoxy" and "halothioalkoxy" refer to -O(haloalkyl) and -S(haloalkyl), respectively. The term "sulfhydryl" refers to -SH.

[0044] The term "aralkyl" refers to an alkyl moiety in which an alkyl hydrogen atom is replaced by an aryl group. One of the carbons of the alkyl moiety serves as the point of attachment of the aralkyl group to another moiety. Any ring or chain atom can be optionally substituted e.g., by one or more substituents. Non-limiting examples of "aralkyl" include benzyl, 2-phenylethyl, and 3 -phenylpropyl groups.

[0045] The term "alkenyl" refers to a straight or branched hydrocarbon chain containing the indicated number of carbon atoms and having one or more carbon -carbon double bonds. Any atom can be optionally substituted, e.g., by one or more substituents. Alkenyl groups can include, e.g., vinyl, allyl, 1-butenyl, and 2-hexenyl.

[0046] The term "heterocycle" or "heterocyclic", as used herein except where noted, represents a stable 4-, 5-, 6- or 7-membered monocyclic- or stable 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered fused bicyclic heterocyclic ring system which comprises at least one non-aromatic ( i.e. saturated or partially unsaturated) ring which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O and S, wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and wherein the nitrogen heteroatom may optionally be quatemized. In the case of a “heterocycle” which is a bicyclic group, the second ring may also be a non-aromatic ring which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O and S, as defined above, or the second ring may be a benzene ring, or a “cycloalkyl”, or a “cycloalkenyl”, as defined immediately below. Examples of such heterocyclic groups include, but are not limited to, azetidine,WSGR Docket No. 53238-724.601chroman, dihydrofuran, dihydropyran, dioxane, dioxolane, hexahydroazepine, imidazolidine, imidazoline, indoline, isochroman, isoindoline, isothiazoline, isothiazolidine, isoxazoline, isoxazolidine, morpholine, oxazoline, oxazolidine, oxetane, piperazine, piperidine, pyran, pyrazolidine, pyrazoline, pyrrolidine, pyrroline, tetrahydrofuran, tetrahydropyran, thiamorpholine, thiazoline, thiazolidine, thiomorpholine and N-oxides thereof.

[0047] The term "cycloalkyl" refers to a fully saturated monocyclic, bicyclic, tricyclic, or other polycyclic hydrocarbon groups. Any atom can be optionally substituted, e.g., by one or more substituents. A ring carbon serves as the point of attachment of a cycloalkyl group to another moiety. Cycloalkyl moieties can include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, and norbomyl (bicycle[2.2.1]heptyl).

[0048] The term "cycloalkenyl" refers to partially unsaturated monocyclic, bicyclic, tricyclic, or other polycyclic hydrocarbon groups. A ring carbon (e.g., saturated or unsaturated) is the point of attachment of the cycloalkenyl substituent. Any atom can be optionally substituted e.g., by one or more substituents. Cycloalkenyl moieties can include, e.g., cyclopentenyl, cyclohexenyl, cyclohexadienyl, or norbomenyl.

[0049] The term "cycloalkylene", as used herein, refers to a divalent monocyclic cycloalkyl group having the indicated number of ring atoms.

[0050] The term "heterocycloalkylene", as used herein, refers to a divalent monocyclic heterocyclyl group having the indicated number of ring atoms.

[0051] The term "aryl" as used herein, is intended to mean any stable monocyclic or bicyclic carbon ring of up to 7 members in each ring, wherein at least one ring is aromatic. Examples of such aryl elements include phenyl, naphthyl, tetrahydronaphthyl, indanyl, or biphenyl.

[0052] The term "heteroaryl", as used herein except where noted, represents a stable 5, 6 or 7-membered monocyclic- or stable 9 or 10-membered fused bicyclic ring system which comprises at least one aromatic ring, -which consists of carbon atoms and from one to three heteroatoms selected from the group consisting of N, O and S wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quatemized. In the case of a “heteroaryl” which is a bicyclic group, the second ring need not be aromatic and need not comprise a heteroatom. Accordingly, “heteroaryl” includes, for example, a stable 5, 6 or 7-membered monocyclic aromatic ring consisting of carbon atoms and from one to four heteroatoms, as defined immediately above, fused to a benzene ring, or fused to a “heterocycle”, “cycloalkyl”, or a “cycloalkenyl”, as defined above. Examples of such heteroaryl groups include, but are not limited to, benzimidazole, benzisothiazole, benzisoxazole, benzofuran, isobenzofuran, benzothiazole, benzothiophene, benzotriazole, benzoxazole, carboline, cinnoline, furan, furazan, imidazole, indazole, indole, indolizine, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, phthalazine, pteridine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and N-oxides thereof.WSGR Docket No. 53238-724.601

[0053] The term "acyl", as used herein, refers to those groups derived from an organic acid by removal of the hydroxy portion of the acid. Accordingly, acyl is meant to include, for example, acetyl, propionyl, butyryl, decanoyl, pivaloyl, benzoyl and the like.COMPOUND FORMS AND SALTS

[0054] The compounds of this disclosure may contain one or more stereocenters and thus occur as racemates and racemic mixtures, enantiomerically-enriched mixtures, single enantiomers, individual diastereomers and diastereomeric mixtures. The compounds of this disclosure may also be represented in multiple tautomeric forms, in such instances, the disclosure expressly includes all tautomeric forms of the compounds described herein, even though only a single tautomeric form may be represented. All such isomeric forms of such compounds are expressly included in the present disclosure. The compounds of this disclosure include the compounds themselves, as well as their salts and their prodrugs, if applicable. A salt, for example, can be formed between an anion and a positively charged substituent (e.g., ammonium) on a compound described herein. Suitable anions include chloride, bromide, iodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, and acetate. Likewise, a salt can also be formed between a cation and a negatively charged substituent (e.g., carboxylate) on a compound described herein. Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and an ammonium cation such as tetramethylammonium ion. As used herein, "pharmaceutically acceptable salts" refer to derivatives wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional nontoxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2 -acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like. When the compound of the present disclosure is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic acid, and the like. In one aspect of the disclosure the salts are citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, fumaric, and tartaric acids. When the compound of the present disclosure is acidic, salts may be prepared from pharmaceutically acceptable non-toxic bases, including inorganic and organic bases. Such salts thatWSGR Docket No. 53238-724.601may be prepared include a lithium salt, sodium salt, potassium salt, magnesium salt, calcium salt, dicyclohexylamine salt, N-methyl-D-glucamine salt, tris(hydroxymethyl)methylamine salt, arginine salt, lysine salt, and the like. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418; Journal of Pharmaceutical Science, 66, 2 (1977); and " Pharmaceutical Salts: Properties, Selection, and Use A Handbook; Wermuth, C. G. and Stahl, P. H. (eds.) Verlag Helvetica Chimica Acta, Zurich, 2002 [ISBN 3-906390-26-8] each of which is incorporated herein by reference in their entireties. The compounds may be radiolabeled with radioactive isotopes, such as for example tritium, iodine -125 or carbon- 14. All isotopic variations of the compounds of the disclosure, whether radioactive or not, are intended to be encompassed within the scope of the disclosure. In some embodiments, hydrogen atoms of the compounds described herein may be replaced with deuterium atoms. In some embodiments, compounds of Formula I are prepared as prodrugs. Prodrugs are generally drug precursors that, following administration to a subject and subsequent absorption, are converted to an active, or a more active species via some process, such as conversion by a metabolic pathway. Examples of prodrugs include Ci-6 alkyl esters of carboxylic acid groups, which, upon administration to a subject, are capable of providing active compounds.PHARMACEUTICAL COMPOSITIONS

[0055] The term "pharmaceutically acceptable carrier" refers to a carrier or adjuvant that may be administered to a patient, together with a compound of this disclosure, or a pharmaceutically acceptable salt thereof, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the compound.

[0056] The term "composition" as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. Such term in relation to pharmaceutical composition, is intended to encompass a product comprising the active ingredient(s), and the inert ingredient(s) that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the pharmaceutical compositions of the present disclosure encompass any composition made by admixing a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. By "pharmaceutically acceptable" it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The present disclosure includes within its scope prodrugs of the compounds of this disclosure. In general, such prodrugs will be functional derivatives of the compounds of this disclosure which are readily convertible in vivo into the required compound. Thus, in the methods of treatment of the present disclosure, the terms "administration of' or "administering a" compound shall encompass the treatment of the variousWSGR Docket No. 53238-724.601conditions described with the compound specifically disclosed or with a compound which may not be specifically disclosed, but which converts to the specified compound in vivo after administration to the patient. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in " Design of Prodrugs," ed. H. Bundgaard, Elsevier, 1985. Metabolites ofthese compounds include active species produced upon introduction of compounds of this disclosure into the biological milieu. The amount administered depends on the compound formulation, route of administration, etc. and is generally empirically determined in routine trials, and variations will necessarily occur depending on the target, the host, and the route of administration, etc. Generally, the quantity of active compound in a unit dose of preparation may be varied or adjusted from about 1, 3, 10 or 30 to about 30, 100, 300 or 1000 mg, according to the particular application. For convenience, the total daily dosage may be divided and administered in portions during the day if desired.

[0057] Disclosed herein is a pharmaceutical composition comprising about 20% weight per weight (w / w) to about 40% (w / w) of 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:O °NN-N(Compound 1), or a pharmaceutically acceptable salt thereof, e.g., about 20% (w / w), 21% (w / w), 22% (w / w), 23% (w / w), 24% (w / w), 25% (w / w), 26% (w / w), 27% (w / w), 28% (w / w), 29% (w / w), 30% (w / w), 31% (w / w), 32% (w / w), 33% (w / w), 34% (w / w), 35% (w / w), 36% (w / w), 37% (w / w), 38% (w / w), 39% (w / w), or 40% (w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 50% (w / w) to about 70% (w / w) of a diluent, e.g., about 50% (w / w), 51% (w / w), 52% (w / w), 53% (w / w), 54% (w / w), 55% (w / w), 56% (w / w), 57% (w / w), 58% (w / w), 59% (w / w), 60% (w / w), 61% (w / w), 62% (w / w), 63% (w / w), 64% (w / w), 65% (w / w), 66% (w / w), 67% (w / w), 68% (w / w), 69% (w / w), or about 70% (w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 5% (w / w) to about 15% (w / w) of a disintegrant, e.g., about 5% (w / w), 5.1% (w / w), 5.2% (w / w), 5.3% (w / w), 5.4% (w / w), 5.5% (w / w), 5.6% (w / w), 5.7% (w / w), 5.8% (w / w), 5.9% (w / w), 6% (w / w), 6.1% (w / w), 6.2% (w / w), 6.3% (w / w), 6.4% (w / w), 6.5% (w / w), 6.6% (w / w), 6.7% (w / w), 6.8% (w / w), 6.9% (w / w), 7% (w / w), 7.1% (w / w), 7.2% (w / w), 7.3% (w / w), 7.4% (w / w), 7.5% (w / w), 7.6% (w / w), 7.7% (w / w), 7.8% (w / w), 7.9% (w / w), 8% (w / w), 8.1% (w / w), 8.2% (w / w), 8.3% (w / w), 8.4% (w / w), 8.5% (w / w), 8.6% (w / w), 8.7% (w / w), 8.8% (w / w), 8.9% (w / w), 9% (w / w), 9.1% (w / w), 9.2% (w / w), 9.3% (w / w), 9.4% (w / w), 9.5% (w / w), 9.6% (w / w), 9.7% (w / w), 9.8% (w / w), 9.9% (w / w), 10% (w / w), 10.1% (w / w), 10.2% (w / w), 10.3% (w / w), 10.4% (w / w), 10.5% (w / w), 10.6% (w / w), 10.7% (w / w), 10.8%WSGR Docket No. 53238-724.601(w / w), 10.9% (w / w), 11% (w / w), 11.1% (w / w), 11.2% (w / w), 11.3% (w / w), 11.4% (w / w), 11.5% (w / w), 11.6% (w / w), 11.7% (w / w), 11.8% (w / w), 11.9% (w / w), 12% (w / w), 12.1% (w / w), 12.2% (w / w), 12.3% (w / w), 12.4% (w / w), 12.5% (w / w), 12.6% (w / w), 12.7% (w / w), 12.8% (w / w), 12.9% (w / w), 13% (w / w), 13.1% (w / w), 13.2% (w / w), 13.3% (w / w), 13.4% (w / w), 13.5% (w / w), 13.6% (w / w), 13.7% (w / w), 13.8% (w / w), 13.9% (w / w), 14% (w / w), 14.1% (w / w), 14.2% (w / w), 14.3% (w / w), 14.4% (w / w), 14.5% (w / w), 14.6% (w / w), 14.7% (w / w), 14.8% (w / w), 14.9% (w / w), or about 15% (w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 0.1% (w / w) to about 2% (w / w) of a lubricant, e.g., about 0.1% (w / w), 0.11% (w / w), 0.12% (w / w), 0.13% (w / w), 0.14% (w / w), 0.15% (w / w), 0.16% (w / w), 0.17% (w / w), 0.18% (w / w), 0.19% (w / w), 0.2% (w / w), 0.21% (w / w), 0.22% (w / w), 0.23% (w / w), 0.24% (w / w), 0.25% (w / w), 0.26% (w / w), 0.27% (w / w), 0.28% (w / w), 0.29% (w / w), 0.3% (w / w), 0.31% (w / w), 0.32% (w / w), 0.33% (w / w), 0.34% (w / w), 0.35% (w / w), 0.36% (w / w), 0.37% (w / w), 0.38% (w / w), 0.39% (w / w), 0.4% (w / w), 0.41% (w / w), 0.42% (w / w), 0.43% (w / w), 0.44% (w / w), 0.45% (w / w), 0.46% (w / w), 0.47% (w / w), 0.48% (w / w), 0.49% (w / w), 0.5% (w / w), 0.51% (w / w), 0.52% (w / w), 0.53% (w / w), 0.54% (w / w), 0.55% (w / w), 0.56% (w / w), 0.57% (w / w), 0.58% (w / w), 0.59% (w / w), 0.6% (w / w), 0.61% (w / w), 0.62% (w / w), 0.63% (w / w), 0.64% (w / w), 0.65% (w / w), 0.66% (w / w), 0.67% (w / w), 0.68% (w / w), 0.69% (w / w), 0.7% (w / w), 0.71% (w / w), 0.72% (w / w), 0.73% (w / w), 0.74% (w / w), 0.75% (w / w), 0.76% (w / w), 0.77% (w / w), 0.78% (w / w), 0.79% (w / w), 0.8% (w / w), 0.81% (w / w), 0.82% (w / w), 0.83% (w / w), 0.84% (w / w), 0.85% (w / w), 0.86% (w / w), 0.87% (w / w), 0.88% (w / w), 0.89% (w / w), 0.9% (w / w), 0.91% (w / w), 0.92% (w / w), 0.93% (w / w), 0.94% (w / w), 0.95% (w / w), 0.96% (w / w), 0.97% (w / w), 0.98% (w / w), 0.99% (w / w), 1% (w / w), 1.01% (w / w), 1.02% (w / w), 1.03% (w / w), 1.04% (w / w), 1.05% (w / w), 1.06% (w / w), 1.07% (w / w), 1.08% (w / w), 1.09% (w / w), 1.1% (w / w), 1.11% (w / w), 1.12% (w / w), 1.13% (w / w), 1.14% (w / w), 1.15% (w / w), 1.16% (w / w), 1.17% (w / w), 1.18% (w / w), 1.19% (w / w), 1.2% (w / w), 1.21% (w / w), 1.22% (w / w), 1.23% (w / w), 1.24% (w / w), 1.25% (w / w), 1.26% (w / w), 1.27% (w / w), 1.28% (w / w), 1.29% (w / w), 1.3% (w / w), 1.31% (w / w), 1.32% (w / w), 1.33% (w / w), 1.34% (w / w), 1.35% (w / w), 1.36% (w / w), 1.37% (w / w), 1.38% (w / w), 1.39% (w / w), 1.4% (w / w), 1.41% (w / w), 1.42% (w / w), 1.43% (w / w), 1.44% (w / w), 1.45% (w / w), 1.46% (w / w), 1.47% (w / w), 1.48% (w / w), 1.49% (w / w), 1.5% (w / w), 1.51% (w / w), 1.52% (w / w), 1.53% (w / w), 1.54% (w / w), 1.55% (w / w), 1.56% (w / w), 1.57% (w / w), 1.58% (w / w), 1.59% (w / w), 1.6% (w / w), 1.61% (w / w), 1.62% (w / w), 1.63% (w / w), 1.64% (w / w), 1.65% (w / w), 1.66% (w / w), 1.67% (w / w), 1.68% (w / w), 1.69% (w / w), 1.7% (w / w), 1.71% (w / w), 1.72% (w / w), 1.73% (w / w), 1.74% (w / w), 1.75% (w / w), 1.76% (w / w), 1.77% (w / w), 1.78% (w / w), 1.79% (w / w), 1.8% (w / w), 1.81% (w / w), 1.82% (w / w), 1.83% (w / w), 1.84% (w / w), 1.85% (w / w), 1.86% (w / w), 1.87% (w / w), 1.88% (w / w), 1.89% (w / w), 1.9% (w / w), 1.91% (w / w), 1.92% (w / w), 1.93% (w / w), 1.94% (w / w), 1.95% (w / w), 1.96% (w / w), 1.97% (w / w), 1.98% (w / w), 1.99% (w / w), or about 2% (w / w), or any concentration therebetween.WSGR Docket No. 53238-724.601

[0058] Disclosed herein is a pharmaceutical composition comprising: about 20% (w / w) to about 40% (w / w) of 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid:0 °NN-N(Compound 1), or a pharmaceutically acceptable salt thereof; about 50% (w / w) to about 70% (w / w) of a diluent; about 5% (w / w) to about 15% (w / w) of a disintegrant; and about 0.1% (w / w) to about 2% (w / w) of a lubricant.

[0059] In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 53%(w / w) and about 67% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 55% (w / w) and about 65% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 63% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 58% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 59% (w / w) and about 61% (w / w). In some embodiments, the diluent comprises a first diluent and a second diluent. In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w). In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w). In some embodiments, the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the first diluent comprises mannitol. In some embodiments, the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises microcrystalline cellulose, lactose. In some embodiments, the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the diluent comprises an intra-granular diluent andWSGR Docket No. 53238-724.601an extra-granular diluent. In some embodiments, the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose. In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w). In some embodiments, the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate.

[0060] In some embodiments, the disintegrant comprises an intra-granular disintegrant and an extra-granular disintegrant. In some embodiments, the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium. In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1.5% (w / w). In some embodiments, the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 26% (w / w) and about 34% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 27% (w / w) and about 33% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 29% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 29% (w / w) and about 31% (w / w). In some embodiments,WSGR Docket No. 53238-724.601the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 31% (w / w) and about 32% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 30% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 31% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 32% (w / w). In some embodiments, the Compound 1 is in a free acid form. In some embodiments, the Compound 1 is in a salt form. In some embodiments, the Compound 1 is a sodium salt.

[0061] In some embodiments, the pharmaceutical composition further comprises a coating layer. In some embodiments, the coating layer comprises an Opadry coating fdm, an Eudragit coating fdm, or methacrylic acid copolymer. In some embodiments, the coating layer comprises pigment, polyvinyl alcohol, Talc, calcium carbonate, and / or sodium lauryl sulfate. In some embodiments, the coating layer is about 1% (w / w) to about 10% (w / w) in the pharmaceutical composition, e.g., about 1% (w / w), 1.1% (w / w), 1.2% (w / w), 1.3% (w / w), 1.4% (w / w), 1.5% (w / w), 1.6% (w / w), 1.7% (w / w), 1.8% (w / w), 1.9% (w / w), 2% (w / w), 2.1% (w / w), 2.2% (w / w), 2.3% (w / w), 2.4% (w / w), 2.5% (w / w), 2.6% (w / w), 2.7% (w / w), 2.8% (w / w), 2.9% (w / w), 3% (w / w), 3.1% (w / w), 3.2% (w / w), 3.3% (w / w), 3.4% (w / w), 3.5% (w / w), 3.6% (w / w), 3.7% (w / w), 3.8% (w / w), 3.9% (w / w), 4% (w / w), 4.1% (w / w), 4.2% (w / w), 4.3% (w / w), 4.4% (w / w), 4.5% (w / w), 4.6% (w / w), 4.7% (w / w), 4.8% (w / w), 4.9% (w / w), 5% (w / w), 5.1% (w / w), 5.2% (w / w), 5.3% (w / w), 5.4% (w / w), 5.5% (w / w), 5.6% (w / w), 5.7% (w / w), 5.8% (w / w), 5.9% (w / w), 6% (w / w), 6.1% (w / w), 6.2% (w / w), 6.3% (w / w), 6.4% (w / w), 6.5% (w / w), 6.6% (w / w), 6.7% (w / w), 6.8% (w / w), 6.9% (w / w), 7% (w / w), 7.1% (w / w), 7.2% (w / w), 7.3% (w / w), 7.4% (w / w), 7.5% (w / w), 7.6% (w / w), 7.7% (w / w), 7.8% (w / w), 7.9% (w / w), 8% (w / w), 8.1% (w / w), 8.2% (w / w), 8.3% (w / w), 8.4% (w / w), 8.5% (w / w), 8.6% (w / w), 8.7% (w / w), 8.8% (w / w), 8.9% (w / w), 9% (w / w), 9.1% (w / w), 9.2% (w / w), 9.3% (w / w), 9.4% (w / w), 9.5% (w / w), 9.6% (w / w), 9.7% (w / w), 9.8% (w / w), 9.9% (w / w), 10% (w / w), 10.1% (w / w), 10.2% (w / w), 10.3% (w / w), 10.4% (w / w), 10.5% (w / w), 10.6% (w / w), 10.7% (w / w), 10.8% (w / w), 10.9% (w / w), 11% (w / w), 11.1% (w / w), 11.2% (w / w), 11.3% (w / w), 11.4% (w / w), 11.5% (w / w), 11.6% (w / w), 11.7% (w / w), 11.8% (w / w), 11.9% (w / w), or about 12% (w / w), or any concentration therebetween. In some embodiments, the coating layer is about 2% (w / w) to about 8% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 3% (w / w) to about 7% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 4% (w / w) to about 6% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 3% (w / w) to about 4% (w / w) in the pharmaceutical composition.

[0062] In some embodiments, the pharmaceutical composition comprises: about 31% (w / w) of the Compound 1; about 59% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; and about 0.5% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 30% (w / w) of the Compound 1; about 31% (w / w) ofWSGR Docket No. 53238-724.601mannitol; about 28% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 28% (w / w) to about 29% (w / w) of the Compound 1; about 29% (w / w) to about 30% (w / w) of mannitol; about 26% (w / w) to about 27% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; about 0.9% (w / w) to about 1% (w / w) of magnesium stearate; and about 3% (w / w) to about 4% (w / w) of the coating layer. In some embodiments, the pharmaceutical composition comprises: about 31% (w / w) to about 32% (w / w) of the Compound 1; about 29% (w / w) to about 30% (w / w) of mannitol; about 28% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1.5% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 28% (w / w) to about 29% (w / w) of the Compound 1; about 27% (w / w) to about 28% (w / w) of mannitol; about 25% (w / w) to about 26% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; about 1% (w / w) to about 1.5% (w / w) of magnesium stearate; and about 7% (w / w) to about 8% (w / w) of the coating layer. In some embodiments, the pharmaceutical composition is a tablet or in a capsule. In some embodiments, the pharmaceutical composition is in a capsule. In some embodiments, the pharmaceutical composition is in a capsule comprising hydroxypropyl methylcellulose (HPMC).

[0063] In some embodiments, the capsule comprises about 25 mg or 100 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the pharmaceutical composition is a tablet. In some embodiments, the pharmaceutical composition is a tablet that is produced through direct compaction. In some embodiments, the pharmaceutical composition is a tablet that is produced through roller compaction. In some embodiments, the tablet comprises about 300 mg or 600 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet comprises about 200 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet is about 500 mg to about 1200 mg, e.g., about 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 660 mg, 670 mg, 680 mg, 690 mg, 700 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, 900 mg, 910 mg, 920 mg, 930 mg, 940 mg, 950 mg, 960 mg, 970 mg, 980 mg, 990 mg, 1000 mg, 1010 mg, 1020 mg, 1030 mg, 1040 mg, 1050 mg, 1060 mg, 1070 mg, 1080 mg, 1090 mg, 1100 mg, 1110 mg, 1120 mg, 1130 mg, 1140 mg, 1150 mg, 1160 mg, 1170 mg, 1180 mg, 1190 mg, or about 1200 mg, or any amount therebetween. In some embodiments, the tablet is about 700 mg to about 750 mg. In some embodiments, the tablet is about 1000 mg to about 1100 mg. In some embodiments, the pharmaceutical composition is administered orally. In some embodiments, the tablet comprises a colorant. In some embodiments, the colorant comprises a pigment. In some embodiments, the tablet comprises an embossed surface.WSGR Docket No. 53238-724.601

[0064] Disclosed herein is a pharmaceutical composition comprising about 50% (w / w) to about 70% (w / w) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-0 °N~Nethoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid:(Compound 1), or a pharmaceutically acceptable salt thereof, e.g., about 50%(w / w), 51%(w / w), 52%(w / w), 53%(w / w), 54%(w / w), 55%(w / w), 56%(w / w), 57%(w / w), 58%(w / w), 59%(w / w), 60%(w / w), 61%(w / w), 62%(w / w), 63%(w / w), 64%(w / w), 65%(w / w), 66%(w / w), 67%(w / w), 68%(w / w), 69%(w / w), or about 70%(w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 15% (w / w) to about 35% (w / w) of a diluent, e.g., about 15%(w / w), 15.5%(w / w), 16%(w / w), 16.5%(w / w), 17%(w / w), 17.5%(w / w), 18%(w / w), 18.5%(w / w), 19%(w / w), 19.5%(w / w), 20%(w / w), 20.5%(w / w), 21%(w / w), 21.5%(w / w), 22%(w / w), 22.5%(w / w), 23%(w / w), 23.5%(w / w), 24%(w / w), 24.5%(w / w), 25%(w / w), 25.5%(w / w), 26%(w / w), 26.5%(w / w), 27%(w / w), 27.5%(w / w), 28%(w / w), 28.5%(w / w), 29%(w / w), 29.5%(w / w), 30%(w / w), 30.5%(w / w), 31%(w / w), 31.5%(w / w), 32%(w / w), 32.5%(w / w), 33%(w / w), 33.5%(w / w), 34%(w / w), 34.5%(w / w), or about 35%(w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 5% (w / w) to about 15% (w / w) of a disintegrant, e.g., about 5.1%(w / w), 5.2%(w / w), 5.3%(w / w), 5.4%(w / w), 5.5%(w / w), 5.6%(w / w), 5.7%(w / w), 5.8%(w / w), 5.9%(w / w), 6%(w / w), 6.1%(w / w), 6.2%(w / w), 6.3%(w / w), 6.4%(w / w), 6.5%(w / w), 6.6%(w / w), 6.7%(w / w), 6.8%(w / w), 6.9%(w / w), 7%(w / w), 7.1%(w / w), 7.2%(w / w), 7.3%(w / w), 7.4%(w / w), 7.5%(w / w), 7.6%(w / w), 7.7%(w / w), 7.8%(w / w), 7.9%(w / w), 8%(w / w), 8.1%(w / w), 8.2%(w / w), 8.3%(w / w), 8.4%(w / w), 8.5%(w / w), 8.6%(w / w), 8.7%(w / w), 8.8%(w / w), 8.9%(w / w), 9%(w / w), 9.1%(w / w), 9.2%(w / w), 9.3%(w / w), 9.4%(w / w), 9.5%(w / w), 9.6%(w / w), 9.7%(w / w), 9.8%(w / w), 9.9%(w / w), I0%(w / w), 10. I%(w / w), I0.2%(w / w), 10.3%(w / w), 10.4%(w / w), 10.5%(w / w), 10.6%(w / w), 10.7%(w / w), 10.8%(w / w), I0.9%(w / w), 11%(w / w), 11.1%(w / w), 11.2%(w / w), 11.3%(w / w), 11.4%(w / w), 11.5%(w / w), 11.6%(w / w), 11.7%(w / w), II.8%(w / w), 11.9%(w / w), 12%(w / w), 12.1%(w / w), 12.2%(w / w), 12.3%(w / w), 12.4%(w / w), 12.5%(w / w), 12.6%(w / w), 12.7%(w / w), 12.8%(w / w), 12.9%(w / w), 13%(w / w), 13.1%(w / w), 13.2%(w / w), 13.3%(w / w), 13.4%(w / w), 13.5%(w / w), 13.6%(w / w), 13.7%(w / w), 13.8%(w / w), 13.9%(w / w), 14%(w / w), 14.1%(w / w), 14.2%(w / w), 14.3%(w / w), 14.4%(w / w), 14.5%(w / w), 14.6%(w / w), 14.7%(w / w), 14.8%(w / w), 14.9%(w / w), or about 15%(w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 0.1% (w / w) to about 2% (w / w) of a lubricant, e.g., about 0.1%(w / w), 0.1 l%(w / w), 0.12%(w / w), 0.13%(w / w), 0.14%(w / w), 0.15%(w / w), 0.16%(w / w), 0.17%(w / w), 0. I8%(w / w), 0.19%(w / w),WSGR Docket No. 53238-724.6010.2%(w / w), 0.21%(w / w), 0.22%(w / w), 0.23%(w / w), 0.24%(w / w), 0.25%(w / w), 0.26%(w / w), 0.27%(w / w), 0.28%(w / w), 0.29%(w / w), 0.3%(w / w), 0.31%(w / w), 0.32%(w / w), 0.33%(w / w), 0.34%(w / w), 0.35%(w / w), 0.36%(w / w), 0.37%(w / w), 0.38%(w / w), 0.39%(w / w), 0.4%(w / w), 0.41%(w / w), 0.42%(w / w), 0.43%(w / w), 0.44%(w / w), 0.45%(w / w), 0.46%(w / w), 0.47%(w / w), 0.48%(w / w), 0.49%(w / w), 0.5%(w / w), 0.51%(w / w), 0.52%(w / w), 0.53%(w / w), 0.54%(w / w), 0.55%(w / w), 0.56%(w / w), 0.57%(w / w), 0.58%(w / w), 0.59%(w / w), 0.6%(w / w), 0.61%(w / w), 0.62%(w / w), 0.63%(w / w), 0.64%(w / w), 0.65%(w / w), 0.66%(w / w), 0.67%(w / w), 0.68%(w / w), 0.69%(w / w), 0.7%(w / w), 0.71%(w / w), 0.72%(w / w), 0.73%(w / w), 0.74%(w / w), 0.75%(w / w), 0.76%(w / w), 0.77%(w / w), 0.78%(w / w), 0.79%(w / w), 0.8%(w / w), 0.81%(w / w), 0.82%(w / w), 0.83%(w / w), 0.84%(w / w), 0.85%(w / w), 0.86%(w / w), 0.87%(w / w), 0.88%(w / w), 0.89%(w / w), 0.9%(w / w), 0.91%(w / w), 0.92%(w / w), 0.93%(w / w), 0.94%(w / w), 0.95%(w / w), 0.96%(w / w), 0.97%(w / w), 0.98%(w / w), 0.99%(w / w), 1%(w / w), 1.01%(w / w), 1.02%(w / w), 1.03%(w / w), 1.04%(w / w), 1.05%(w / w), 1.06%(w / w), 1.07%(w / w), 1.08%(w / w), 1.09%(w / w), 1.1%(w / w), 1.11%(w / w), 1.12%(w / w), 1.13%(w / w), 1.14%(w / w), 1.15%(w / w), 1.16%(w / w), 1.17%(w / w), 1.18%(w / w), 1.19%(w / w), 1.2%(w / w), 1.21%(w / w), 1.22%(w / w), 1.23%(w / w), 1.24%(w / w), 1.25%(w / w), 1.26%(w / w), 1.27%(w / w), 1.28%(w / w), 1.29%(w / w), 1.3%(w / w), 1.31%(w / w), 1.32%(w / w), 1.33%(w / w), 1.34%(w / w), 1.35%(w / w), 1.36%(w / w), 1.37%(w / w), 1.38%(w / w), 1.39%(w / w), 1.4%(w / w), 1.41%(w / w), 1.42%(w / w), 1.43%(w / w), 1.44%(w / w), 1.45%(w / w), 1.46%(w / w), 1.47%(w / w), 1.48%(w / w), 1.49%(w / w), 1.5%(w / w), 1.51%(w / w), 1.52%(w / w), 1.53%(w / w), 1.54%(w / w), 1.55%(w / w), 1.56%(w / w), 1.57%(w / w), 1.58%(w / w), 1.59%(w / w), 1.6%(w / w), 1.61%(w / w), 1.62%(w / w), 1.63%(w / w), 1.64%(w / w), 1.65%(w / w), 1.66%(w / w), 1.67%(w / w), 1.68%(w / w), 1.69%(w / w), 1.7%(w / w), 1.71%(w / w), 1.72%(w / w), 1.73%(w / w), 1.74%(w / w), 1.75%(w / w), 1.76%(w / w), 1.77%(w / w), 1.78%(w / w), 1.79%(w / w), 1.8%(w / w), 1.81%(w / w), 1.82%(w / w), 1.83%(w / w), 1.84%(w / w), 1.85%(w / w), 1.86%(w / w), 1.87%(w / w), 1.88%(w / w), 1.89%(w / w), 1.9%(w / w), 1.91%(w / w), 1.92%(w / w), 1.93%(w / w), 1.94%(w / w), 1.95%(w / w), 1.96%(w / w), 1.97%(w / w), 1.98%(w / w), 1.99%(w / w), or about 2%(w / w), or any concentration therebetween.

[0065] Disclosed herein is a pharmaceutical composition comprising: (a) about 50% (w / w) to about 70% (w / w) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-0 °NN~N4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:(Compound 1), or a pharmaceutically acceptable salt thereof; (b) about 15% (w / w) to about 35% (w / w) of a diluent; (c)WSGR Docket No. 53238-724.601about 5% (w / w) to about 15% (w / w) of a disintegrant; and (d) about 0.1% (w / w) to about 2% (w / w) of a lubricant.

[0066] In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 16% (w / w) and about 34% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 17% (w / w) and about 33% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 18% (w / w) and about 32% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 19% (w / w) and about 31% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 20% (w / w) and about 30% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 21 % (w / w) and about 29% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 22% (w / w) and about 28% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 23% (w / w) and about 27% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 24% (w / w) and about 26% (w / w). In some embodiments, the diluent comprises a first diluent and a second diluent. In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 5% (w / w) and about 15% (w / w). In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 10% (w / w) and about 15% (w / w). In some embodiments, the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises silicified microcrystalline cellulose. In some embodiments, first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the diluent comprises an intra-granular diluent and an extra-granular diluent. In some embodiments, the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose. In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 10% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w). In some embodiments, the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate. In some embodiments, the disintegrant comprises an intra-WSGR Docket No. 53238-724.601granular disintegrant and an extra-granular disintegrant. In some embodiments, the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium. In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1% (w / w). In some embodiments, the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 62% (w / w) and about 63% (w / w). In some embodiments, the Compound 1 is in a free acid form. In some embodiments, the Compound 1 is in a salt form. In some embodiments, the Compound 1 is a sodium salt.

[0067] In some embodiments, the pharmaceutical composition comprises: about 62% (w / w) to about 63% (w / w) of the Compound 1; about 13% (w / w) to about 14% (w / w) of mannitol; about 12% (w / w) to about 13% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition is a tablet. In some embodiments, the pharmaceutical composition is a tablet that is produced through roller compaction. In some embodiments, the tablet comprises about 300 mg to about 350 mg of the Compound 1 in a free acid form or a molar equivalent thereof, e.g., about 300 mg, 305 mg, 310 mg, 315 mg, 320 mg, 325 mg, 330 mg, 335 mg, 340 mg, 345 mg, or about 350 mg, or any amount therebetween. In some embodiments, the tablet comprises about 600 mg to about 650 mg of the Compound 1 in a free acid form or a molar equivalent thereof, e.g., about 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, or about 650 mg, or any amount therebetween. In some embodiments, the tablet is about 500 mg to about 1000 mg, e.g., about 500 mg,WSGR Docket No. 53238-724.601510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 660 mg, 670 mg, 680 mg, 690 mg, 700 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, 900 mg, 910 mg, 920 mg, 930 mg, 940 mg, 950 mg, 960 mg, 970 mg, 980 mg, 990 mg, or about 1000 mg, or any amount therebetween. In some embodiments, the tablet is about 500 mg. In some embodiments, the tablet is about 1000 mg. In some embodiments, the pharmaceutical composition is administered orally. In some embodiments, the tablet comprises a colorant. In some embodiments, the colorant comprises a pigment. In some embodiments, the tablet comprises an embossed surface.METHODS OF USES

[0068] In one aspect the disclosure disclosed herein is directed to compounds of Formula I and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. In another aspect the disclosure is directed to a method of preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers. The disclosure also includes pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula I, or a pharmaceutically acceptable salt thereof. The disclosure disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The disclosure disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a therapeutically effective amount of a selective PPARa antagonist. The methods include administering to the subject an effective amount of a compound of Formula (I) (and / or a compound of any of the other formulae described herein) or a salt (e.g., a pharmaceutically acceptable salt) thereof as defined anywhere herein. In another aspect, the use of a compound of Formula (I) (and / or a compound of any of the other formulae described herein) or a salt (e.g., a pharmaceutically acceptable salt) thereof as defined anywhere herein in the preparation of, or for use as, a medicament for the treatment (e.g., controlling, alleviating, or slowing the progression of) or prevention (e.g., delaying the onset of or reducing the risk of developing) of one or more diseases, disorders, or conditions caused by, or associated with, prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers.

[0069] In one aspect the disclosure is directed a method of treating a cancer which is negatively impacted by diminution in its metabolism via fatty acid oxidation, comprising administration of a therapeutically effective amount of a compound of Formula I (and / or a compound of any of the other formulae described herein) or a salt (e.g., a pharmaceutically acceptable salt). In another aspect, the disclosure is directed to a method of treating a cancer having a metabolism that is reliant on fatty acidWSGR Docket No. 53238-724.601oxidation, comprising administration of a therapeutically effective amount of a compound of Formula I (and / or a compound of any of the other formulae described herein), or a pharmaceutically acceptable salt thereof.

[0070] Disclosed herein is a method of treating cancer in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition disclosed herein.

[0071] In some embodiments, the cancer comprises hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), renal cell carcinoma (RCC), colorectal cancer (CRC), pancreatic cancer (PANC), prostate cancer, non-small cell lung cancer (NSCLC), or metastatic castration-resistant prostate cancer (mCRPC). In some embodiments, the method of claim further comprises administering to the subject a second therapy. In some embodiments, the administering comprises administering orally. In some embodiments, the administering comprises administering orally a granule of the pharmaceutical composition, wherein a dispenser comprising a pouch or sachet contains the granule of the pharmaceutical composition.

[0072] In some embodiments, the pharmaceutical composition comprises about 20% weight per weight (w / w) to about 40% (w / w) of 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:O °NN-N(Compound 1), or a pharmaceutically acceptable salt thereof, e.g., about 20% (w / w), 21% (w / w), 22% (w / w), 23% (w / w), 24% (w / w), 25% (w / w), 26% (w / w), 27% (w / w), 28% (w / w), 29% (w / w), 30% (w / w), 31% (w / w), 32% (w / w), 33% (w / w), 34% (w / w), 35% (w / w), 36% (w / w), 37% (w / w), 38% (w / w), 39% (w / w), or 40% (w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 50% (w / w) to about 70% (w / w) of a diluent, e.g., about 50% (w / w), 51% (w / w), 52% (w / w), 53% (w / w), 54% (w / w), 55% (w / w), 56% (w / w), 57% (w / w), 58% (w / w), 59% (w / w), 60% (w / w), 61% (w / w), 62% (w / w), 63% (w / w), 64% (w / w), 65% (w / w), 66% (w / w), 67% (w / w), 68% (w / w), 69% (w / w), or about 70% (w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 5% (w / w) to about 15% (w / w) of a disintegrant, e.g., about 5% (w / w), 5.1% (w / w), 5.2% (w / w), 5.3% (w / w), 5.4% (w / w), 5.5% (w / w), 5.6% (w / w), 5.7% (w / w), 5.8% (w / w), 5.9% (w / w), 6% (w / w), 6.1% (w / w), 6.2% (w / w), 6.3% (w / w), 6.4% (w / w), 6.5% (w / w), 6.6% (w / w), 6.7% (w / w), 6.8% (w / w), 6.9% (w / w), 7% (w / w), 7.1% (w / w), 7.2% (w / w), 7.3% (w / w), 7.4% (w / w), 7.5% (w / w), 7.6% (w / w), 7.7% (w / w), 7.8% (w / w), 7.9% (w / w), 8% (w / w), 8.1% (w / w), 8.2% (w / w), 8.3% (w / w), 8.4% (w / w), 8.5% (w / w), 8.6% (w / w), 8.7% (w / w), 8.8% (w / w), 8.9% (w / w), 9% (w / w), 9.1% (w / w), 9.2% (w / w), 9.3%WSGR Docket No. 53238-724.601(w / w), 9.4% (w / w), 9.5% (w / w), 9.6% (w / w), 9.7% (w / w), 9.8% (w / w), 9.9% (w / w), 10% (w / w), 10.1% (w / w), 10.2% (w / w), 10.3% (w / w), 10.4% (w / w), 10.5% (w / w), 10.6% (w / w), 10.7% (w / w), 10.8% (w / w), 10.9% (w / w), 11% (w / w), 11.1% (w / w), 11.2% (w / w), 11.3% (w / w), 11.4% (w / w), 11.5% (w / w), 11.6% (w / w), 11.7% (w / w), 11.8% (w / w), 11.9% (w / w), 12% (w / w), 12.1% (w / w), 12.2% (w / w), 12.3% (w / w), 12.4% (w / w), 12.5% (w / w), 12.6% (w / w), 12.7% (w / w), 12.8% (w / w), 12.9% (w / w), 13% (w / w), 13.1% (w / w), 13.2% (w / w), 13.3% (w / w), 13.4% (w / w), 13.5% (w / w), 13.6% (w / w), 13.7% (w / w), 13.8% (w / w), 13.9% (w / w), 14% (w / w), 14.1% (w / w), 14.2% (w / w), 14.3% (w / w), 14.4% (w / w), 14.5% (w / w), 14.6% (w / w), 14.7% (w / w), 14.8% (w / w), 14.9% (w / w), or about 15% (w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 0.1% (w / w) to about 2% (w / w) of a lubricant, e.g., about 0.1% (w / w), 0.11% (w / w), 0.12% (w / w), 0.13% (w / w), 0.14% (w / w), 0.15% (w / w), 0.16% (w / w), 0.17% (w / w), 0.18% (w / w), 0.19% (w / w), 0.2% (w / w), 0.21% (w / w), 0.22% (w / w), 0.23% (w / w), 0.24% (w / w), 0.25% (w / w), 0.26% (w / w), 0.27% (w / w), 0.28% (w / w), 0.29% (w / w), 0.3% (w / w), 0.31% (w / w), 0.32% (w / w), 0.33% (w / w), 0.34% (w / w), 0.35% (w / w), 0.36% (w / w), 0.37% (w / w), 0.38% (w / w), 0.39% (w / w), 0.4% (w / w), 0.41% (w / w), 0.42% (w / w), 0.43% (w / w), 0.44% (w / w), 0.45% (w / w), 0.46% (w / w), 0.47% (w / w), 0.48% (w / w), 0.49% (w / w), 0.5% (w / w), 0.51% (w / w), 0.52% (w / w), 0.53% (w / w), 0.54% (w / w), 0.55% (w / w), 0.56% (w / w), 0.57% (w / w), 0.58% (w / w), 0.59% (w / w), 0.6% (w / w), 0.61% (w / w), 0.62% (w / w), 0.63% (w / w), 0.64% (w / w), 0.65% (w / w), 0.66% (w / w), 0.67% (w / w), 0.68% (w / w), 0.69% (w / w), 0.7% (w / w), 0.71% (w / w), 0.72% (w / w), 0.73% (w / w), 0.74% (w / w), 0.75% (w / w), 0.76% (w / w), 0.77% (w / w), 0.78% (w / w), 0.79% (w / w), 0.8% (w / w), 0.81% (w / w), 0.82% (w / w), 0.83% (w / w), 0.84% (w / w), 0.85% (w / w), 0.86% (w / w), 0.87% (w / w), 0.88% (w / w), 0.89% (w / w), 0.9% (w / w), 0.91% (w / w), 0.92% (w / w), 0.93% (w / w), 0.94% (w / w), 0.95% (w / w), 0.96% (w / w), 0.97% (w / w), 0.98% (w / w), 0.99% (w / w), 1% (w / w), 1.01% (w / w), 1.02% (w / w), 1.03% (w / w), 1.04% (w / w), 1.05% (w / w), 1.06% (w / w), 1.07% (w / w), 1.08% (w / w), 1.09% (w / w), 1.1% (w / w), 1.11% (w / w), 1.12% (w / w), 1.13% (w / w), 1.14% (w / w), 1.15% (w / w), 1.16% (w / w), 1.17% (w / w), 1.18% (w / w), 1.19% (w / w), 1.2% (w / w), 1.21% (w / w), 1.22% (w / w), 1.23% (w / w), 1.24% (w / w), 1.25% (w / w), 1.26% (w / w), 1.27% (w / w), 1.28% (w / w), 1.29% (w / w), 1.3% (w / w), 1.31% (w / w), 1.32% (w / w), 1.33% (w / w), 1.34% (w / w), 1.35% (w / w), 1.36% (w / w), 1.37% (w / w), 1.38% (w / w), 1.39% (w / w), 1.4% (w / w), 1.41% (w / w), 1.42% (w / w), 1.43% (w / w), 1.44% (w / w), 1.45% (w / w), 1.46% (w / w), 1.47% (w / w), 1.48% (w / w), 1.49% (w / w), 1.5% (w / w), 1.51% (w / w), 1.52% (w / w), 1.53% (w / w), 1.54% (w / w), 1.55% (w / w), 1.56% (w / w), 1.57% (w / w), 1.58% (w / w), 1.59% (w / w), 1.6% (w / w), 1.61% (w / w), 1.62% (w / w), 1.63% (w / w), 1.64% (w / w), 1.65% (w / w), 1.66% (w / w), 1.67% (w / w), 1.68% (w / w), 1.69% (w / w), 1.7% (w / w), 1.71% (w / w), 1.72% (w / w), 1.73% (w / w), 1.74% (w / w), 1.75% (w / w), 1.76% (w / w), 1.77% (w / w), 1.78% (w / w), 1.79% (w / w), 1.8% (w / w), 1.81% (w / w), 1.82% (w / w), 1.83% (w / w), 1.84% (w / w), 1.85% (w / w), 1.86% (w / w), 1.87% (w / w), 1.88% (w / w), 1.89% (w / w), 1.9% (w / w), 1.91% (w / w), 1.92% (w / w), 1.93% (w / w), 1.94%WSGR Docket No. 53238-724.601(w / w), 1.95% (w / w), 1.96% (w / w), 1.97% (w / w), 1.98% (w / w), 1.99% (w / w), or about 2% (w / w), or any concentration therebetween.

[0073] In some embodiments, the pharmaceutical composition comprises: about 20% (w / w) to about 40% (w / w) of 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:0 °NN~N(Compound 1), or a pharmaceutically acceptable salt thereof; about 50% (w / w) to about 70% (w / w) of a diluent; about 5% (w / w) to about 15% (w / w) of a disintegrant; and about 0.1% (w / w) to about 2% (w / w) of a lubricant.

[0074] In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 53%(w / w) and about 67% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 55% (w / w) and about 65% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 63% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 58% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 59% (w / w) and about 61% (w / w). In some embodiments, the diluent comprises a first diluent and a second diluent. In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w). In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w). In some embodiments, the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the first diluent comprises mannitol. In some embodiments, the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises microcrystalline cellulose, lactose. In some embodiments, the second diluent comprises silicified microcrystalline cellulose. In someWSGR Docket No. 53238-724.601embodiments, the first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the diluent comprises an intra-granular diluent and an extra-granular diluent. In some embodiments, the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose. In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w). In some embodiments, the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate.

[0075] In some embodiments, the disintegrant comprises an intra-granular disintegrant and an extra-granular disintegrant. In some embodiments, the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium. In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1.5% (w / w). In some embodiments, the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 26% (w / w) and about 34% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 27% (w / w) and about 33% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 29% (w / w). In someWSGR Docket No. 53238-724.601embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 29% (w / w) and about 31% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 31% (w / w) and about 32% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 30% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 31% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 32% (w / w). In some embodiments, the Compound 1 is in a free acid form. In some embodiments, the Compound 1 is in a salt form. In some embodiments, the Compound 1 is a sodium salt.

[0076] In some embodiments, the pharmaceutical composition further comprises a coating layer. In some embodiments, the coating layer comprises an Opadry coating fdm, an Eudragit coating fdm, or methacrylic acid copolymer. In some embodiments, the coating layer comprises pigment, polyvinyl alcohol, Talc, calcium carbonate, and / or sodium lauryl sulfate. In some embodiments, the coating layer is about 1% (w / w) to about 10% (w / w) in the pharmaceutical composition, e.g., about 1% (w / w), 1.1% (w / w), 1.2% (w / w), 1.3% (w / w), 1.4% (w / w), 1.5% (w / w), 1.6% (w / w), 1.7% (w / w), 1.8% (w / w), 1.9% (w / w), 2% (w / w), 2.1% (w / w), 2.2% (w / w), 2.3% (w / w), 2.4% (w / w), 2.5% (w / w), 2.6% (w / w), 2.7% (w / w), 2.8% (w / w), 2.9% (w / w), 3% (w / w), 3.1% (w / w), 3.2% (w / w), 3.3% (w / w), 3.4% (w / w), 3.5% (w / w), 3.6% (w / w), 3.7% (w / w), 3.8% (w / w), 3.9% (w / w), 4% (w / w), 4.1% (w / w), 4.2% (w / w), 4.3% (w / w), 4.4% (w / w), 4.5% (w / w), 4.6% (w / w), 4.7% (w / w), 4.8% (w / w), 4.9% (w / w), 5% (w / w), 5.1% (w / w), 5.2% (w / w), 5.3% (w / w), 5.4% (w / w), 5.5% (w / w), 5.6% (w / w), 5.7% (w / w), 5.8% (w / w), 5.9% (w / w), 6% (w / w), 6.1% (w / w), 6.2% (w / w), 6.3% (w / w), 6.4% (w / w), 6.5% (w / w), 6.6% (w / w), 6.7% (w / w), 6.8% (w / w), 6.9% (w / w), 7% (w / w), 7.1% (w / w), 7.2% (w / w), 7.3% (w / w), 7.4% (w / w), 7.5% (w / w), 7.6% (w / w), 7.7% (w / w), 7.8% (w / w), 7.9% (w / w), 8% (w / w), 8.1% (w / w), 8.2% (w / w), 8.3% (w / w), 8.4% (w / w), 8.5% (w / w), 8.6% (w / w), 8.7% (w / w), 8.8% (w / w), 8.9% (w / w), 9% (w / w), 9.1% (w / w), 9.2% (w / w), 9.3% (w / w), 9.4% (w / w), 9.5% (w / w), 9.6% (w / w), 9.7% (w / w), 9.8% (w / w), 9.9% (w / w), 10% (w / w), 10.1% (w / w), 10.2% (w / w), 10.3% (w / w), 10.4% (w / w), 10.5% (w / w), 10.6% (w / w), 10.7% (w / w), 10.8% (w / w), 10.9% (w / w), 11% (w / w), 11.1% (w / w), 11.2% (w / w), 11.3% (w / w), 11.4% (w / w), 11.5% (w / w), 11.6% (w / w), 11.7% (w / w), 11.8% (w / w), 11.9% (w / w), or about 12% (w / w), or any concentration therebetween. In some embodiments, the coating layer is about 2% (w / w) to about 8% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 3% (w / w) to about 7% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 4% (w / w) to about 6% (w / w) in the pharmaceutical composition. In some embodiments, the coating layer is about 3% (w / w) to about 4% (w / w) in the pharmaceutical composition.

[0077] In some embodiments, the pharmaceutical composition comprises: about 31% (w / w) of the Compound 1; about 59% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10%WSGR Docket No. 53238-724.601(w / w) of croscarmellose sodium; and about 0.5% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 30% (w / w) of the Compound 1; about 31% (w / w) of mannitol; about 28% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 28% (w / w) to about 29% (w / w) of the Compound 1; about 29% (w / w) to about 30% (w / w) of mannitol; about 26% (w / w) to about 27% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; about 0.9% (w / w) to about 1% (w / w) of magnesium stearate; and about 3% (w / w) to about 4% (w / w) of the coating layer. In some embodiments, the pharmaceutical composition comprises: about 31% (w / w) to about 32% (w / w) of the Compound 1; about 29% (w / w) to about 30% (w / w) of mannitol; about 28% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1.5% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition comprises: about 28% (w / w) to about 29% (w / w) of the Compound 1; about 27% (w / w) to about 28% (w / w) of mannitol; about 25% (w / w) to about 26% (w / w) of silicified microcrystalline cellulose; about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; about 1% (w / w) to about 1.5% (w / w) of magnesium stearate; and about 7% (w / w) to about 8% (w / w) of the coating layer. In some embodiments, the pharmaceutical composition is a tablet or in a capsule. In some embodiments, the pharmaceutical composition is in a capsule. In some embodiments, the pharmaceutical composition is in a capsule comprising hydroxypropyl methylcellulose (HPMC).

[0078] In some embodiments, the capsule comprises about 25 mg or 100 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the pharmaceutical composition is a tablet. In some embodiments, the pharmaceutical composition is a tablet that is produced through direct compaction. In some embodiments, the pharmaceutical composition is a tablet that is produced through roller compaction. In some embodiments, the tablet comprises about 300 mg or 600 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet comprises about 200 mg of the Compound 1 in a free acid form or a molar equivalent thereof. In some embodiments, the tablet is about 500 mg to about 1200 mg, e.g., about 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 660 mg, 670 mg, 680 mg, 690 mg, 700 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, 900 mg, 910 mg, 920 mg, 930 mg, 940 mg, 950 mg, 960 mg, 970 mg, 980 mg, 990 mg, 1000 mg, 1010 mg, 1020 mg, 1030 mg, 1040 mg, 1050 mg, 1060 mg, 1070 mg, 1080 mg, 1090 mg, 1100 mg, 1110 mg, 1120 mg, 1130 mg, 1140 mg, 1150 mg, 1160 mg, 1170 mg, 1180 mg, 1190 mg, or about 1200 mg, or any amount therebetween. In some embodiments, the tablet is about 700 mg to about 750 mg. In some embodiments, the tablet is about 1000 mg to about 1100 mg. In some embodiments, the pharmaceutical composition is administered orally.WSGR Docket No. 53238-724.601

[0079] In some embodiments, the pharmaceutical composition comprises about 50% (w / w) to about 70% (w / w) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-0 °N.N~N4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:(Compound 1), or a pharmaceutically acceptable salt thereof, e.g., about 50%(w / w), 51%(w / w), 52%(w / w), 53%(w / w), 54%(w / w), 55%(w / w), 56%(w / w), 57%(w / w), 58%(w / w), 59%(w / w), 60%(w / w), 61%(w / w), 62%(w / w), 63%(w / w), 64%(w / w), 65%(w / w), 66%(w / w), 67%(w / w), 68%(w / w), 69%(w / w), or about 70%(w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 15% (w / w) to about 35% (w / w) of a diluent, e.g., about 15%(w / w), 15.5%(w / w), 16%(w / w), 16.5%(w / w), 17%(w / w), 17.5%(w / w), 18%(w / w), 18.5%(w / w), 19%(w / w), 19.5%(w / w), 20%(w / w), 20.5%(w / w), 21%(w / w), 21.5%(w / w), 22%(w / w), 22.5%(w / w), 23%(w / w), 23.5%(w / w), 24%(w / w), 24.5%(w / w), 25%(w / w), 25.5%(w / w), 26%(w / w), 26.5%(w / w), 27%(w / w), 27.5%(w / w), 28%(w / w), 28.5%(w / w), 29%(w / w), 29.5%(w / w), 30%(w / w), 30.5%(w / w), 31%(w / w), 31.5%(w / w), 32%(w / w), 32.5%(w / w), 33%(w / w), 33.5%(w / w), 34%(w / w), 34.5%(w / w), or about 35%(w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 5% (w / w) to about 15% (w / w) of a disintegrant, e.g., about 5.1%(w / w), 5.2%(w / w), 5.3%(w / w), 5.4%(w / w), 5.5%(w / w), 5.6%(w / w), 5.7%(w / w), 5.8%(w / w), 5.9%(w / w), 6%(w / w), 6.1%(w / w), 6.2%(w / w), 6.3%(w / w), 6.4%(w / w), 6.5%(w / w), 6.6%(w / w), 6.7%(w / w), 6.8%(w / w), 6.9%(w / w), 7%(w / w), 7.1%(w / w), 7.2%(w / w), 7.3%(w / w), 7.4%(w / w), 7.5%(w / w), 7.6%(w / w), 7.7%(w / w), 7.8%(w / w), 7.9%(w / w), 8%(w / w), 8.1%(w / w), 8.2%(w / w), 8.3%(w / w), 8.4%(w / w), 8.5%(w / w), 8.6%(w / w), 8.7%(w / w), 8.8%(w / w), 8.9%(w / w), 9%(w / w), 9.1%(w / w), 9.2%(w / w), 9.3%(w / w), 9.4%(w / w), 9.5%(w / w), 9.6%(w / w), 9.7%(w / w), 9.8%(w / w), 9.9%(w / w), 10%(w / w), 10.1%(w / w), 10.2%(w / w), 10.3%(w / w), 10.4%(w / w), 10.5%(w / w), 10.6%(w / w), 10.7%(w / w), 10.8%(w / w), 10.9%(w / w), 11%(w / w), 11.1%(w / w), 11.2%(w / w), 11.3%(w / w), 11.4%(w / w), 11.5%(w / w), 11.6%(w / w), 11.7%(w / w), 11.8%(w / w), 11.9%(w / w), 12%(w / w), 12.1%(w / w), 12.2%(w / w), 12.3%(w / w), 12.4%(w / w), 12.5%(w / w), 12.6%(w / w), 12.7%(w / w), 12.8%(w / w), 12.9%(w / w), 13%(w / w), 13.1%(w / w), 13.2%(w / w), 13.3%(w / w), 13.4%(w / w), 13.5%(w / w), 13.6%(w / w), 13.7%(w / w), 13.8%(w / w), 13.9%(w / w), 14%(w / w), 14.1%(w / w), 14.2%(w / w), 14.3%(w / w), 14.4%(w / w), 14.5%(w / w), 14.6%(w / w), 14.7%(w / w), 14.8%(w / w), 14.9%(w / w), or about 15%(w / w), or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises about 0.1% (w / w) to about 2% (w / w) of a lubricant, e.g., about 0.1%(w / w), 0.1 l%(w / w), 0.12%(w / w), 0.13%(w / w), 0.14%(w / w), 0.15%(w / w), 0.16%(w / w), 0.17%(w / w), 0.18%(w / w), 0.19%(w / w),WSGR Docket No. 53238-724.6010.2%(w / w), 0.21%(w / w), 0.22%(w / w), 0.23%(w / w), 0.24%(w / w), 0.25%(w / w), 0.26%(w / w), 0.27%(w / w), 0.28%(w / w), 0.29%(w / w), 0.3%(w / w), 0.31%(w / w), 0.32%(w / w), 0.33%(w / w), 0.34%(w / w), 0.35%(w / w), 0.36%(w / w), 0.37%(w / w), 0.38%(w / w), 0.39%(w / w), 0.4%(w / w), 0.41%(w / w), 0.42%(w / w), 0.43%(w / w), 0.44%(w / w), 0.45%(w / w), 0.46%(w / w), 0.47%(w / w), 0.48%(w / w), 0.49%(w / w), 0.5%(w / w), 0.51%(w / w), 0.52%(w / w), 0.53%(w / w), 0.54%(w / w), 0.55%(w / w), 0.56%(w / w), 0.57%(w / w), 0.58%(w / w), 0.59%(w / w), 0.6%(w / w), 0.61%(w / w), 0.62%(w / w), 0.63%(w / w), 0.64%(w / w), 0.65%(w / w), 0.66%(w / w), 0.67%(w / w), 0.68%(w / w), 0.69%(w / w), 0.7%(w / w), 0.71%(w / w), 0.72%(w / w), 0.73%(w / w), 0.74%(w / w), 0.75%(w / w), 0.76%(w / w), 0.77%(w / w), 0.78%(w / w), 0.79%(w / w), 0.8%(w / w), 0.81%(w / w), 0.82%(w / w), 0.83%(w / w), 0.84%(w / w), 0.85%(w / w), 0.86%(w / w), 0.87%(w / w), 0.88%(w / w), 0.89%(w / w), 0.9%(w / w), 0.91%(w / w), 0.92%(w / w), 0.93%(w / w), 0.94%(w / w), 0.95%(w / w), 0.96%(w / w), 0.97%(w / w), 0.98%(w / w), 0.99%(w / w), 1%(w / w), 1.01%(w / w), 1.02%(w / w), 1.03%(w / w), 1.04%(w / w), 1.05%(w / w), 1.06%(w / w), 1.07%(w / w), 1.08%(w / w), 1.09%(w / w), 1.1%(w / w), 1.11%(w / w), 1.12%(w / w), 1.13%(w / w), 1.14%(w / w), 1.15%(w / w), 1.16%(w / w), 1.17%(w / w), 1.18%(w / w), 1.19%(w / w), 1.2%(w / w), 1.21%(w / w), 1.22%(w / w), 1.23%(w / w), 1.24%(w / w), 1.25%(w / w), 1.26%(w / w), 1.27%(w / w), 1.28%(w / w), 1.29%(w / w), 1.3%(w / w), 1.31%(w / w), 1.32%(w / w), 1.33%(w / w), 1.34%(w / w), 1.35%(w / w), 1.36%(w / w), 1.37%(w / w), 1.38%(w / w), 1.39%(w / w), 1.4%(w / w), 1.41%(w / w), 1.42%(w / w), 1.43%(w / w), 1.44%(w / w), 1.45%(w / w), 1.46%(w / w), 1.47%(w / w), 1.48%(w / w), 1.49%(w / w), 1.5%(w / w), 1.51%(w / w), 1.52%(w / w), 1.53%(w / w), 1.54%(w / w), 1.55%(w / w), 1.56%(w / w), 1.57%(w / w), 1.58%(w / w), 1.59%(w / w), 1.6%(w / w), 1.61%(w / w), 1.62%(w / w), 1.63%(w / w), 1.64%(w / w), 1.65%(w / w), 1.66%(w / w), 1.67%(w / w), 1.68%(w / w), 1.69%(w / w), 1.7%(w / w), 1.71%(w / w), 1.72%(w / w), 1.73%(w / w), 1.74%(w / w), 1.75%(w / w), 1.76%(w / w), 1.77%(w / w), 1.78%(w / w), 1.79%(w / w), 1.8%(w / w), 1.81%(w / w), 1.82%(w / w), 1.83%(w / w), 1.84%(w / w), 1.85%(w / w), 1.86%(w / w), 1.87%(w / w), 1.88%(w / w), 1.89%(w / w), 1.9%(w / w), 1.91%(w / w), 1.92%(w / w), 1.93%(w / w), 1.94%(w / w), 1.95%(w / w), 1.96%(w / w), 1.97%(w / w), 1.98%(w / w), 1.99%(w / w), or about 2%(w / w), or any concentration therebetween.

[0080] In some embodiments, the pharmaceutical composition comprises: (a) about 50% (w / w) to about 70% (w / w) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-0 °NN~Nyl)propyl)-4-ethoxy-[l, l'-biphenyl]-3-yl)acetic acid:(Compound 1), or a pharmaceutically acceptable salt thereof; (b) about 15% (w / w) to about 35% (w / w) of a diluent;WSGR Docket No. 53238-724.601(c) about 5% (w / w) to about 15% (w / w) of a disintegrant; and (d) about 0.1% (w / w) to about 2% (w / w) of a lubricant.

[0081] In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 16% (w / w) and about 34% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 17% (w / w) and about 33% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 18% (w / w) and about 32% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 19% (w / w) and about 31% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 20% (w / w) and about 30% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 21 % (w / w) and about 29% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 22% (w / w) and about 28% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 23% (w / w) and about 27% (w / w). In some embodiments, the amount of the diluent in the pharmaceutical composition is between about 24% (w / w) and about 26% (w / w). In some embodiments, the diluent comprises a first diluent and a second diluent. In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 5% (w / w) and about 15% (w / w). In some embodiments, the amount of the first or second diluent in the pharmaceutical composition is between about 10% (w / w) and about 15% (w / w). In some embodiments, the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate. In some embodiments, the second diluent comprises silicified microcrystalline cellulose. In some embodiments, first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose. In some embodiments, the diluent comprises an intra-granular diluent and an extra-granular diluent. In some embodiments, the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose. In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 10% (w / w). In some embodiments, the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w). In some embodiments, the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate. In some embodiments, the disintegrant comprises an intra-WSGR Docket No. 53238-724.601granular disintegrant and an extra-granular disintegrant. In some embodiments, the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium. In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w). In some embodiments, the amount of the lubricant in the pharmaceutical composition is about 1% (w / w). In some embodiments, the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w). In some embodiments, the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 62% (w / w) and about 63% (w / w). In some embodiments, the Compound 1 is in a free acid form. In some embodiments, the Compound 1 is in a salt form. In some embodiments, the Compound 1 is a sodium salt.

[0082] In some embodiments, the pharmaceutical composition comprises: about 62% (w / w) to about 63% (w / w) of the Compound 1; about 13% (w / w) to about 14% (w / w) of mannitol; about 12% (w / w) to about 13% (w / w) of silicified microcrystalline cellulose; about 10% (w / w) of croscarmellose sodium; and about 1% (w / w) of magnesium stearate. In some embodiments, the pharmaceutical composition is a tablet. In some embodiments, the pharmaceutical composition is a tablet that is produced through roller compaction. In some embodiments, the tablet comprises about 300 mg to about 350 mg of the Compound 1 in a free acid form or a molar equivalent thereof, e.g., about 300 mg, 305 mg, 310 mg, 315 mg, 320 mg, 325 mg, 330 mg, 335 mg, 340 mg, 345 mg, or about 350 mg, or any amount therebetween. In some embodiments, the tablet comprises about 600 mg to about 650 mg of the Compound 1 in a free acid form or a molar equivalent thereof, e.g., about 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, or about 650 mg, or any amount therebetween. In some embodiments, the tablet is about 500 mg to about 1000 mg, e.g., about 500 mg,WSGR Docket No. 53238-724.601510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 660 mg, 670 mg, 680 mg, 690 mg, 700 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, 900 mg, 910 mg, 920 mg, 930 mg, 940 mg, 950 mg, 960 mg, 970 mg, 980 mg, 990 mg, or about 1000 mg, or any amount therebetween. In some embodiments, the tablet is about 500 mg. In some embodiments, the tablet is about 1000 mg. In some embodiments, the pharmaceutical composition is administered orally.

[0083] In one aspect, a method for treating cancer is disclosed herein. In some embodiments, the method comprises administering to a subject in need thereof a compound of Formula I:D6B AlJR5YR1R2 KFormula Ior a pharmaceutically acceptable salt thereof.

[0084] In some embodiments, Al is phenyl, pyrimidinyl, or pyridinyl;A2 is A2aR9A2awherein A2a is phenyl or pyridinyl;X is selected from the group consisting of -(CH₂)₂-, -(CH₂)₃-, or -(CH2)4-, each optionally mono- or di-substituted with halogen;Y is O;R1and R2are each independently selected from the group consisting of:(a) hydrogen,(b) halogen,(c) -O-(R7),(d) CF3,(e) -Ci-ealkyl,R3is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,(c) -O-(R7), andWSGR Docket No. 53238-724.601(d) -N(R7)S(=O)2(R8),wherein the alkyl portion of choice (b) is optionally substituted with halogen or hydroxyl; R4and R4are each independently selected from the group consisting of:(a) hydrogen,(b) -O-R7,(c) -C(R7)(R8)OH,(d) -C1-6alkyl-C(=O)OH,(e) -C3-6cycloalkyl-C(=O)OH,(f) -C(=O)OH,(g) -NHS(=O)2N(R7)(R8),(h) -Cs-ecycloalkyl,(i) -CF3,(j) -heterocycle,(k) -Ci -ealkyl, and(l) halogen;with the proviso that at least one of R3, R4and R4is other than hydrogen;R5is selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,(c) -C1-4alkyl(R7),wherein the alkyl portion of choices (b) and (c) is optionally substituted with halogen or Ci-4alkyl;R6is selected from the group consisting of:(a) -Ci -ealkylaryl,(b) -C1-6alkylheteroaryl, and(c) Ci-4alkyl(R7);wherein the alkyl portion of choices (a), (b), and (c) is optionally substituted with halogen or Ci.4alkyl, andwherein the aryl portion of choice (a), and the heteroaryl portion of choice (b) are optionally mono- or di-substituted with substituents selected from the group consisting of halogen, nitro, -CF3, Ci-ealkyl, Ci-ealkoxy, halo Ci-ealkyl, Ckecycloalkyl. Ci-. cycloalkoxy. aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH( Ci-ealkyl), -NH(C3-ecycloalkyl), -N(Ci-ealkyl)2, -N(C3-6cycloalkyl)2, -S(=O)oCi-6alkyl, S(=O)oC3-6cycloalkyl, and CN, wherein each o is independently 0, 1, or 2;R7and R8are each independently selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,WSGR Docket No. 53238-724.601(c) -Cs-ecycloalkyl,(d) -aryl,(e) -heteroaryl, and(f) CF3; andR9and R10are each independently selected from the group consisting of:(a) hydrogen,(b) -C1-6alkyl,(c) halogen,(d) CF3, and(e) Ci-ealkoxywherein the alkyl of choice (b) is optionally mono-, di- or tri-substituted with halogen.

[0085] In some embodiments, X is -CH2CH2CH2- or -CF2CH2CH2-. In some embodiments, Al is phenyl, and R1 and R2 are each hydrogen. In some embodiments, A2 is A2a and A2a is phenyl.

[0086] In some embodiments, R3 is selected from the group consisting of: hydrogen,(a) -O-(R7),(b) -N(R7)S(=O)2(R8), and(c) -Cl-6alkyl; andR4 and R4’ are each independently selected from the group consisting of:(a) hydrogen,(b) -O-(R7),(c) -C(R7)(R8)OH,(d) -CI-6alkyl-C(=O)OH,(e) -C3-6cycloalkyl-C(=O)OH,(f) -C(=O)OH,(g) C3-6cycloalkyl,(h) CF3,(i) heterocycle,(j) -Cl-6alkyl, and(k) halogen.

[0087] In some embodiments, R4 and R4’ are each independently selected from the group consisting of:(a) -C(R7)(R8)OH,(b) (b) -O-(R7),(c) (c) -CI-6alkyl-C(=O)OH,(d) (d) -C(=O)OH,(e) (e) -C3-6cycloalkyl,(f) (f) CF3,WSGR Docket No. 53238-724.601(g) (g) heterocycle,(h) (h) -Cl-6alkyl, and(i) (i) halogen;R5 is selected from the group consisting of:(a) hydrogen,(b) -Cl-6alkyl, and(c) -Cl-4alkyl(R7); andR6 is selected from the group consisting of:(a) -Cl-6alkylaryl,(b) -Cl-6alkylheteroaryl, and(c) -Cl-6alkyl(R7); andwherein the aryl portion of choice (a), and the heteroaryl portion of choice (b) are optionally mono- or di-substituted with substituents selected from the group consisting of halogen, nitro, -CF3, Cl-6alkyl, Cl-6alkoxy, halo Cl-6alkyl, C3-6cycloalkyl, C3-6cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, -NH(Cl-6alkyl), -NH(C3-6cycloalkyl), -N(Cl-6alkyl)2, -N(C3-6cycloalkyl)2, and CN.

[0088] In some embodiments, wherein the compound of Formula (I) is a compound of Formula lb:Formula lbor a pharmaceutically acceptable salt thereof.

[0089] In some embodiments, the compound of Formula (I) is selected from the group comprising: (a) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[l,r- biphenyl] -3 -yl)acetic acid;(b) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[l,r- biphenyl] -4-yl)acetic acid;(c) 3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)[l,r- biphenyl] -3 -carboxylic acid;(d) 3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)[l,r- biphenyl]-4-carboxylic acid;(e) l-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- ethoxy-[ 1, 1 '-biphenyl] -3-yl)cyclopropanecarboxylic acid;(f) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- ethoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid;WSGR Docket No. 53238-724.601(g) l-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[l,l'- biphenyl] -3 -yl)cyclopropanecarboxylic acid;(h) l-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[l,l'- biphenyl]-4-yl)cyclopropanecarboxylic acid;(i) 3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- methoxy-[ 1, 1 '-biphenyl] -3 -carboxylic acid;(j) 3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy- [1,1 '-biphenyl] -3 -carboxylic acid;(k) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- propoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid;(l) N-(6-(3 -(3 -( 1 -(4-(tert-butyl)benzyl)-4-ethyl-5 -oxo-4, 5 -dihydro- 1H- 1,2,4-triazol-3 - yl)propyl)phenyl)pyridin-3 -yl)benzenesulfonamide;(m) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- methoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid;(n) l-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- methyl-[l,l'-biphenyl]-3-yl)cyclopropanecarboxylic acid;(o) 2-(4-(benzyloxy)-3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3- yl)propyl)-[ 1, 1 '-biphenyl] -3-yl)acetic acid;(p) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- (cyclopropylmethoxy)-[ 1, 1 '-biphenyl] -3-yl)acetic acid;(q) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- fluoro-[l, l'-biphenyl]-3-yl)acetic acid;(r) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-6- ethoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid;(s) 3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- propoxy-[ 1, 1 '-biphenyl] -3 -carboxylic acid;(t) N-((3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-[l,l'- biphenyl] -3 -yl)methyl)benzene sulfonamide;(u) 3-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- methoxy- [1,1 '-biphenyl] -3 -yl)propanoic acid;(v) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)-l,l- difluoropropyl)-4-ethoxy-[ 1, 1 '-biphenyl] -3-yl)acetic acid;(w) N-(6-(3-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)-l,l- difluoropropyl) phenyl)pyridin-3 -yl)benzene sulfonamide;(x) 2-(5-(6-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3- yl)propyl)pyridin-2-yl)-2-methoxyphenyl)acetic acid;WSGR Docket No. 53238-724.601(y) 3-(3-(3'-(lH-tetrazol-5-yl)-[l,l'-biphenyl]-3-yl)propyl)-l-(4-(tert-butyl)benzyl)-4-ethyl-lH-l,2,4- triazol -5 (4H) -one;(z) 2-(5-(4-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3- yl)propyl)pyrimidin-2-yl)-2-ethoxyphenyl)acetic acid;(aa)2-(5-(6-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3- yl)propyl)pyrimidin-4-yl)-2-ethoxyphenyl)acetic acid;(bb) (3 '-(3 -( 1 -(4-(tert-butyl)benzyl)-4-ethyl-5 -oxo-4, 5 -dihydro- 1H- 1,2,4-triazol-3 -yl)propyl)-3 - methoxy-[ 1, 1 '-biphenyl] -4-yl)acetic acid;(cc)(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-3-ethoxy- [1,1 '-biphenyl] -4-yl)acetic acid;(dd) (3 '-(3 -( 1 -(4-(tert-butyl)benzyl)-4-ethyl-5 -oxo-4, 5 -dihydro- 1H- 1,2,4-triazol-3 -yl)propyl)-3 - propoxy-[ 1, 1 '-biphenyl] -4-yl)acetic acid;(ee)2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-3- hydroxy-[ 1, 1 '-biphenyl] -4-yl)acetic acid;(ff) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- isopropoxy-[l,l'-biphenyl]-3-yl)acetic acid; and(gg) 2-(3'-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4- (2-(dimethylamino)ethoxy)-[l, l'-biphenyl]-3-yl)acetic acid,or a pharmaceutically acceptable salt of any of the foregoing.

[0090] In some embodiments, the compound of Formula (I) has the structure:WSGR Docket No. 53238-724.601WSGR Docket No. 53238-724.601WSGR Docket No. 53238-724.601WSGR Docket No. 53238-724.601, or

[0091] In some embodiments, the compound of Formula (I) has the structure:WSGR Docket No. 53238-724.601WSGR Docket No. 53238-724.601WSGR Docket No. 53238-724.601

[0092] In some embodiments, the compound of Formula (I) has the structure:WSGR Docket No. 53238-724.601

[0093] In some embodiments, the compound of Formula (I) has the structure:WSGR Docket No. 53238-724.601

[0094] In some embodiments, the method disclosed herein may be used for treatment or prevention of prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. In some embodiments, the method disclosed herein may be used for preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers. In some embodiments, the method disclosed herein may be used for treatment or prevention of prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. In some embodiments, the cancer is selected from the group comprising breast cancer, colon cancer, prostate cancer, pancreatic cancer, leukemia, lymphoma, ovarian cancers, neuroblastoma, glioblastoma, kidney cancer, bladder cancer, gastrointestinal stromal tumors, liver cancer, head and neck cancer, lung cancer, melanoma, or a hematological malignancy. In certain embodiments, the cancer is refractory, non-responsive, or resistant to chemotherapy and / or haploidentical stem cell transplantation. In some embodiments, the cancer is a metastatic or non-metastatic cancer. In some embodiments, the cancer is an advanced cancer. In some embodiments, the cancer is selected from the group comprising bladder cancer, breast cancer, metastatic breast cancer, colon cancer, rectal cancer, metastatic colorectal cancer, endometrial cancer, cervical cancer, uterine cancer, ovarian cancer, kidney cancer, liver cancer, leukemia, lung cancer (both small cell and nonsmall cell), squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, melanoma, Lewis lung carcinoma, non-Hodgkin lymphoma, pancreatic cancer, testicular cancer, prostate cancer, thyroid cancer, sarcoma (including osteosarcoma), esophageal cancer, gastric cancer, head and neck cancer, lung cancer melanoma, myeloma, neuroblastoma, glioblastoma, and cancers of the brain. In some embodiments, the cancer is selected the group comprising colorectal cancer (CRC), pancreatic cancer (PANC), cholangiocarcinoma (CCA), prostate cancer, hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC). In some embodiments, the cancer is metastatic castration-resistant prostate cancer (mCRPC). In some embodiments, the cancer is anWSGR Docket No. 53238-724.601advanced cancer or a metastatic cancer. In some embodiments, the cancer is an advanced or metastatic solid tumor.ADMINISTRATION

[0095] The compounds and compositions described herein can, for example, be administered orally, parenterally (e.g., subcutaneously, intracutaneously, intravenously, intramuscularly, intraarticularly, intraarterially, intrasynovially, intrastemally, intrathecally, intralesionally and by intracranial injection or infusion techniques), by inhalation spray, topically, rectally, nasally, buccally, vaginally, via an implanted reservoir, by injection, subdermally, intraperitoneally, transmucosally, or in an ophthalmic preparation, with a dosage ranging from about 0.01 mg / kg to about 1000 mg / kg, (e.g., from about 0.01 to about 100 mg / kg, from about 0.1 to about 100 mg / kg, from about 1 to about 100 mg / kg, from about 1 to about 10 mg / kg) every 4 to 120 hours, or according to the requirements of the particular drug. The interrelationship of dosages for animals and humans (based on milligrams per meter squared of body surface) is described by Freireich et al., Cancer Chemother. Rep. 50, 219 (1966). Body surface area may be approximately determined from height and weight of the patient. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardsley, N. Y., 537 (1970). In certain embodiments, the compositions are administered by oral administration or by injection. The methods herein include the administration of an effective amount of compound or compound composition to achieve the desired or stated effect. Typically, the pharmaceutical compositions of this disclosure will be administered from about 1 to about 6 times per day or alternatively, as a continuous infusion. Such administration can be used as a chronic or acute therapy. Lower or higher doses than those recited above may be required. Specific dosage and treatment regimens for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health status, sex, diet, time of administration, rate of excretion, drug combination, the severity and course of the disease, condition or symptoms, the patient's disposition to the disease, condition or symptoms, and the judgment of the treating physician. Dosage forms include from about 0.05 milligrams to about 2,000 milligrams (e.g., from about 0.1 milligrams to about 1,000 milligrams, from about 0.1 milligrams to about 500 milligrams, from about 0.1 milligrams to about 250 milligrams, from about 0.1 milligrams to about 100 milligrams, from about 0.1 milligrams to about 50 milligrams, or from about 0.1 milligrams to about 25 milligrams) of a compound of Formula I (and / or a compound of any of the other formulae described herein) or a salt (e.g., a pharmaceutically acceptable salt) thereof as defined anywhere herein. The dosage forms can further include a pharmaceutically acceptable carrier and / or an additional therapeutic agent. In one aspect the compounds of the disclosure may be co-administered with one or more additional anti-cancer agents. The additional anti-cancer agents include, but are not limited to alkylating agents such as cyclophosphamide, chlorambucil, mecloreethamine, ifosfamide, or melphalan; antimetabolites such as methotrexate, cytarabine, fludarabine, 6 -mercaptopurine, azathioprene, pyrimidines, or 5 -fluorouracil; antimitotic agents such as vincristine, paclitaxel,WSGR Docket No. 53238-724.601vinorelbine or docetaxel; a topoisomerase inhibitors such as doxorubicin or irinotecan; platinum derivatives such as cisplatin, carboplatin or oxaliplatin; hormone therapeutics such as tamoxifen; aromatase inhibitors such as bicalutamide, anastrozole, exemestane or letrozole; signaling inhibitors such as imatinib, gefitinib or erlotinib; monoclonal antibodies such as rituximab, trastuzumab, gemtuzumab or ozogamicin; differentiating agents such as tretinoin or arsenic trioxide; antiangiogenic agents such as bevacizumab, sorafenib, or sunitinib; biologic response modifiers such as interferonalpha; topoisomerase inhibitors such as camptothecins (including irinotecan and topotecan), amsacrine, etoposide, etoposide phosphate, orteniposide; cytotoxic antibiotics such as actinomycin, anthracyclines including doxorubicin, daunorubicin, valrubicin, idarubicin, epirubicin, bleomycin, plicamycin or mitomycin; vinca alkaloids such as vincristine, vinblastine, vinorelbine or vindesine; or podophyllotoxins such as etoposide and teniposide; or mTOR inhibitors such as rapamycin, temsirolimus and everolimus.

[0096] Other anti -cancer agents for use in combination with the compounds include one or more of the following: abiraterone, adriamycin, dactinomycin, bleomycin, vinblastine, cisplatin, acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; ametantrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; bleomycin sulfate; brequinar sodium; bropirimine; busulfan; cactinomycin; calusterone; caracemide; carbetimer; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefmgol; chlorambucil; cirolemycin; cladribine; crisnatol mesylate; cyclophosphamide; cytarabine; dacarbazine; daunorubicin hydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguanine mesylate; diaziquone; doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate; eflomithine hydrochloride; elsamitrucin; enloplatin; enpromate; epipropidine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; estramustine phosphate sodium; etanidazole; etoposide; etoposide phosphate; etoprine; everolimus; fadrozole hydrochloride; fazarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; flurocitabine; fosquidone; fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; iopofosine; interleukin II (including recombinant interleukin II, or rlL2), interferon alfa-2a; interferon alfa-2b; interferon alfa-nl; interferon alfa-n3; interferon beta-1 a; interferon gamma-1 b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; liarozole hydrochloride; lometrexol sodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine; metformin, methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin; mitocromin; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran; pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide; pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimerWSGR Docket No. 53238-724.601sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin hydrochloride; pyrazofurin; rapamycin; riboprine; rogletimide; safingol; safingol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talisomycin; tecogalan sodium; tegafur; teloxantrone hydrochloride; temoporfin; temsirolimus; teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracil mustard; uredepa; vapreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; zorubicin hydrochloride.

[0097] In certain embodiments, the additional agents may be administered separately, as part of a multiple dose regimen, from the compounds of this disclosure (e.g., sequentially, or on different overlapping schedules with the administration of one or more compounds of Formula (I) (and / or a compound of any of the other formulae including any subgenera or specific compounds thereof)). In other embodiments, these agents may be part of a single dosage form, mixed together with the compounds of this disclosure in a single composition. In still another embodiment, these agents can be given as a separate dose that is administered at about the same time as one or more compounds of Formula (I) (and / or a compound of any of the other formulae including any subgenera or specific compounds thereof) are administered (e.g., simultaneously with the administration of one or more compounds of Formula (I) (and / or a compound of any of the other formulae including any subgenera or specific compounds thereof)). When the compositions of this disclosure include a combination of a compound of the formulae described herein and one or more additional therapeutic or prophylactic agents, both the compound and the additional agent can be present at dosage levels of between about 1 to 100%, and more preferably between about 5 to 95% of the dosage normally administered in a monotherapy regimen.

[0098] The compositions of this disclosure may contain any conventional non -toxic pharmaceutically-acceptable carriers, adjuvants or vehicles. In some cases, the pH of the formulation may be adjusted with pharmaceutically acceptable acids, bases or buffers to enhance the stability of the formulated compound or its delivery form. The compositions of this disclosure may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, emulsions and aqueous suspensions, dispersions and solutions. In the case of tablets for oral use, carriers which are commonly used include lactose and com starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried com starch. When aqueous suspensions and / or emulsions are administered orally, the active ingredient may be suspended or dissolved in an oily phase that is then combined with emulsifying and / or suspending agents. If desired, certain sweetening and / or flavoring and / or coloring agents may be added.WSGR Docket No. 53238-724.601EXAMPLES

[0099] The following examples are given for the purpose of illustrating various embodiments of the disclosure and are not meant to limit the present disclosure in any fashion. The present examples, along with the methods described herein are presently representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the disclosure. Changes therein and other uses which are encompassed within the spirit of the disclosure as defined by the scope of the claims will occur to those skilled in the art.EXAMPLE 1: Capsule Formulations of Compound 1

[0100] This example illustrates the capsule formulations of Compound 1.

[0101] Chemical Name of Compound 1: Sodium 2-(3'-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro- 1H- 1,2,4-triazol-3 -yl)propyl)-4-ethoxy-[ 1, 1 '-biphenyl] -3 -yl)acetate

[0102] Structure of Compound 1:

[0103] Description and Composition of Compound 1 Drug Product

[0104] 25 mg and / or 100 mg capsules of Compound 1 were developed. Patients were orally administered Compound 1 as solid dose capsules having strengths of 25 mg and 100 mg Compound 1 (free acid) (refer to Table 1 and Table 2). Drug product (Compound 1 capsules) is stored at 2°C to 8°C.

[0105] Table 1 and Table 2 list the composition of Compound 1 capsules, 25 mg and 100 mg, respectively.Table 1: Composition of Compound 1 Capsule, 25 mgComponent %w / w mg per capsule Compound 1 31.0 25.01Silicified Microcrystalline Cellulose (SMCC 90) 59.047.61Croscarmellose Sodium (Ac-Di-Sol) 9.5 7.7 Magnesium Stearate 0.5 0.4White Opaque HPMC Capsule Shell, Size 4 NA1 capsuleTotal 100 80.7N / A: not applicable1Compound 1 free acid. Target quantities of Compound 1 (as sodium salt) and SMCC 90 may be adjusted based on potency of Compound 1WSGR Docket No. 53238-724.601Table 2: Composition of Compound 1 Capsule, 100 mgComponent %w / w mg per capsule Compound 1 31.0 100.01Silicified Microcrystalline Cellulose59.0 190.3(SMCC 90)1Croscarmellose Sodium (Ac-Di-Sol) 9.5 30.6 Magnesium Stearate 0.5 1.6White Opaque HPMC Capsule Shell, SizeNA 1 capsuleOelTotal 100.0 322.6N / A: not applicable1Compound 1 free acid. Target quantities of Compound 1 (as sodium salt) and SMCC 90 may be adjusted based on potency of Compound 1

[0106] The drug product is manufactured by dry blending the excipients (with optional co-milling of API), followed by encapsulation of the dry blend into capsules. The API may be co-milled prior to blending with the excipients, if needed. A description of the manufacturing step are described below. After the blend is prepared, capsules are filled to the proper target weight, 80.7 mg and 322.6 mg, for the 25 mg and 100 mg, respectively.

[0107] Table 3: Manufacturing Process of Compound 1 Capsule, 25 mg and 100 mgThe 25 mg and 100 mg Compound 1 capsules are manufactured under conditions as described below.ProcessingProcess DetailsStepsStep 1 All ingredients were dispensed.Silicified Microcrystalline Cellulose (SMCC 90) was added to the blender and blended Step 2for 1 minute.Compound 1 and Croscarmellose Sodium (Ac-Di-Sol) were added to the blender and Step 3blended for approximately 10 to 15 minutes.Step 3 materials were co-milled through an 032R screen at approximately 1300 Step 4rotations per minute (rpm).The milled blend from step 4 was added back into the blender and blended for Step 5approximately 10 to 15 minutes.Step 5 materials were co-milled through an 032R screen at approximately 1300 Step 6rotations per minute (rpm).Step 7 The milled blend from step 6 was added back into the blender.Magnesium stearate was sieved and added to the blend and mixed in the blender for Step 8approximately 5 minutes.Final blend from Step 8 was encapsulated using the Torpac Pro-filler (25 mg-size 4 Step 9capsule, 100 mg-size Oel capsule).WSGR Docket No. 53238-724.601EXAMPLE 2: Direct Compression Tablets of Compound 1

[0108] This example illustrates a tablet of Compound 1 made by direct compression.

[0109] This example describes the development of 300 mg tablets of Compound 1. The drug product development was carried out for immediate -release core tablet as well as film coated tablets in single strength containing 300 mg of Compound 1. The composition contains Compound 1 as active ingredient, mannitol (Pearlitol 200SD) and silicified microcrystalline cellulose (SMCC HD 90) as diluents, croscarmellose sodium as a disintegrant and magnesium stearate as a lubricant. For coating the tablet, Opadry TF Moisture barrier 217A18002 was used. Dry blending followed by direct compression was selected as the manufacturing process, which consists of Co-Milling-I, blending, Co-Milling-II, lubrication compression, and coating

[0110] Table 4: Composition of Direct Compression Coated Tablets, 300mgCoated tablets Batch NumberSr. No. Ingredients %w / w mg / tab1. Compound I128.851300.0012. Mannitol (Pearlitol 200 SD)129.811310.001Silicified Microcrystalline Cellulose (SMCC HD3. 26.92 280.0090)4. Croscarmellose sodium (Ac-Di-Sol) 9.61 100.005. Magnesium stearate (Veg-grade) 0.96 10.00Core tablet weight 96.15 10006. Opadry TF Moisture barrier 271 Al 80002 White 3.85 40.00Coated tablet weight 100.00 10401Compound 1 free acid. Target quantities of Compound 1 (as sodium salt) and Mannitol may be adjusted based on potency of Compound 1

[0111] Table 5: Manufacturing Process of Direct Compression Coated Tablets, 300 mg ProcessingProcess DetailsStepsProcess for Core tabletCompound 1 API, mannitol, silicified microcrystalline cellulose and croscarmellose Step 1sodium were co-milled through 1.00 mm (1016 pm) quadro co-mill screen.WSGR Docket No. 53238-724.601ProcessingProcess DetailsStepsStep 2 Step 1 material was mixed in 1.9L blender for 10 minutes at 23 rpm.Step 3 Step 2 material was again milled through 1.00 mm (1016 pm) quadro co-mill screen.Magnesium stearate was passed through ASTM #40 sieve and added it in step 3 Step 4material and mixed for 3 minutes at 23 rpm.Compression of above lubricated blend was performed using punches of different Step 5size.Process for Coated tabletsBinder preparation: Opadry TF moisture barrier powder was steadily added to Step 6purified water with stirring to make a 20% w / w dispersion.Step 7 Coating performed on core tablets to get 4% w / w coating.

[0112] EXAMPLE 3: Roller Compaction Tablet of Compound 1

[0113] This example illustrates a tablet of Compound 1 by roller compaction process, tablet, 200mg, 300mg and 600 mg of Compound 1 by roller compaction process. The drug product development was carried out for immediate-release core tablet as well as film coated tablets in varying strengths containing 200mg, 300 mg and 600mg of Compound 1. The composition contains Compound 1 as active ingredient, mannitol (Pearlitol 200SD) and silicified microcrystalline cellulose (SMCC HD 90) as diluents, croscarmellose sodium as a disintegrant and magnesium stearate as a lubricant. For coating the tablet, Opadry TF Moisture barrier 217A18002 was used. Dry blending followed by roller compression was selected as the manufacturing process, which consists of Co-sifting, pre-compaction blending, roller compaction, extragranular blending and lubrication, tablet compression and coating. Various compositions of coating (4%, 6%, 8%) were also evaluated for Compound 1 tablet, 200mg.

[0114] Table 6: Composition of Roller Compaction Coated Tablets, 200mg, 300mg and 600mgWSGR Docket No. 53238-724.601%w / w mg / tab mg / tab mg / tab Sr.Ingredient (600 mg (300 mg (200 mg No.strength) strength) strength) Intragranular (pre-compaction)1. Compound 1' 62.37 623.7341311.8671207.91312. Mannitol (Pearlitol 200 SD)' 13.991 139.900169.9501197.0901Silicified Microcrystalline cellulose 6.32 120.00 3. 63.185 31.593(SMCC HD90)4. Croscarmellose sodium (Ac-Di-Sol) 7.00 70.000 35.000 40.00 5. Magnesium stearate 0.50 5.000 2.500 5.00Extra granularSilicified Microcrystalline cellulose 6.32 66.670 6. 63.185 31.593(SMCC HD90)7. Croscarmellose sodium (Ac-Di-Sol) 3.00 30.000 15.000 26.670Lubrication (Final Blend)8. Magnesium stearate 0.50 5.000 2.50 3.340Total weight of core tablet 100.0 1000.00 500.00 666.681Compound 1 free acid. Target quantities of Compound 1 (as sodium salt) and Mannitol may be adjusted based on potency of Compound 1

[0115] Table 7: Manufacturing Process of Compound 1, 200mg, 300 mg and 600 mg Tablets by Roller CompactionProcessingProcess DetailsStepsProcess for Core tabletCompound 1 API, mannitol, silicified microcrystalline cellulose and croscarmellose Step 1sodium were co-milled through ASTM #30 sieve.Step 2 Step 1 material was mixed in 3L blender for 20 minutes at 23 rpm.Magnesium stearate was passed through ASTM #40 sieve and added it in step 2 Step 3material and mixed for 5 minutes at 23 rpm.Roller compact the Step 3 material and mill through pre -granulator screen (2.50- Step 43.15mm) and fine granulator screen (1.00-1.25mm).Extragranular components were added to Step 4 material and mixed for lOmin at Step 523rpm.Magnesium stearate was passed through ASTM #40 sieve and added it in step 2 Step 6material and mixed for 5 minutes at 23 rpm.Step 6 lubricated blend was compressed for 200mg, 300 mg and 600 mg tablet Step 7strengths by rotary tablet press.

[0116] Table 8: Composition of Roller Compaction Coated Tablets, 200mgWSGR Docket No. 53238-724.601mg / tab Sr. No. Ingredient %w / w(200 mg strength) Intragranular (pre-compaction)1. Compound 1' 31.191207.9112. Mannitol (Pearlitol 200 SD)' 29.311195.421Silicified Microcrystalline cellulose (SMCC3. 18.00 120.0HD90)4. Croscarmellose sodium (Ac-Di-Sol) 6.0 40.00 5. Magnesium stearate 0.75 5.00Extra granularSilicified Microcrystalline cellulose (SMCC6. 10.0 66.67HD90)7. Croscarmellose sodium (Ac-Di-Sol) 4.00 26.67Lubrication (Final Blend)8. Magnesium stearate 0.75 5.0Total weight of core tablet 100.0 666.674% Film Coating9. Opadry White 271 Al 80002 RES 4 26.67 10 Purified Water2NA NA Total weight of coated tablet 104.0 693.346% Film Coating9 Opadry White 271 Al 80002 RES 6 40.00 10 Purified Water2NA NA Total weight of coated tablet 106.0 706.678% Film Coating9 Opadry White 271 Al 80002 RES 8 53.33 10 Purified Water2NA NA Total weight of coated tablet 108.0 720.001Compound 1 free acid. Target quantities of Compound 1 (as sodium salt) and Mannitol may be adjusted based on potency of Compound 12Purified water is removed during coating processWSGR Docket No. 53238-724.601

[0117] Table 9: Manufacturing process of Compound 1 200 mg Coated Tablet by Roller Compaction ProcessingProcess DetailsStepsProcess for Coated tabletCompound 1 API, mannitol, silicified microcrystalline cellulose and croscarmellose Step 1sodium were co-milled through 600 or 1000 pm sieve.Step 2 Step 1 material was mixed in bin blender for 15 minutes at 23 rpm.Magnesium stearate was passed through ASTM #40 sieve and added it in step 2 Step 3material and mixed for 5 minutes at 23 rpm.Roller compact the Step 3 material and mill through pre -granulator screen 2.55mm Step 4and fine granulator screen 0.8mm.Extragranular components were added to Step 4 material and mixed for lOmin at Step 523rpm.Magnesium stearate was passed through ASTM #40 sieve and added it in step 2 Step 6material and mixed for 5 minutes at 23 rpm.Step 7 Step 6 lubricated blend was compressed for 200 mg strength by rotary tablet press. Step 8 20% Opadry TF coating solution was prepared in purified water.Step 9 200mg tablets were coated up to achieve desired weight gain, 4% or 6% or 8%.

[0118] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. WSGR Docket No. 53238-724.601CLAIMS WHAT IS CLAIMED IS:

1. A pharmaceutical composition comprising:(a) about 20% (w / w) to about 40% (w / w) of 2-(3'-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5- oxo-4, 5-dihydro- 1H- 1,2,4-triazol-3-yl)propyl)-4-ethoxy-[ 1, 1 '-biphenyl] -3 -yl)acetic acid:thereof;(b) about 50% (w / w) to about 70% (w / w) of a diluent;(c) about 5% (w / w) to about 15% (w / w) of a disintegrant; and(d) about 0.1% (w / w) to about 2% (w / w) of a lubricant.

2. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w).

3. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 53%(w / w) and about 67% (w / w).

4. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w).

5. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 55% (w / w) and about 65% (w / w).

6. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w).

7. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 63% (w / w).

8. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w).

9. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 57% (w / w) and about 58% (w / w).

10. The pharmaceutical composition of claim 1, wherein the amount of the diluent in the pharmaceutical composition is between about 59% (w / w) and about 61% (w / w).

11. The pharmaceutical composition of any one of claims 1-10, wherein the diluent comprises a first diluent and a second diluent.WSGR Docket No. 53238-724.60112. The pharmaceutical composition of claim 11, wherein the amount of the first or second diluent in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w).

13. The pharmaceutical composition of claim 11, wherein the amount of the first or second diluent in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w).

14. The pharmaceutical composition of any one of claims 11-13, wherein the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate.

15. The pharmaceutical composition of any one of claims 11-14, wherein the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate.

16. The pharmaceutical composition of any one of claims 11-15, wherein the second diluent comprises silicified microcrystalline cellulose.

17. The pharmaceutical composition of any one of claims 11-16, wherein the first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose.

18. The pharmaceutical composition of any one of claims 1-17, wherein the diluent comprises an intra-granular diluent and an extra-granular diluent.

19. The pharmaceutical composition of any one of claims 1-18, wherein the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose.

20. The pharmaceutical composition of any one of claims 1-19, wherein the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w).

21. The pharmaceutical composition of any one of claims 1-19, wherein the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w).

22. The pharmaceutical composition of any one of claims 1-19, wherein the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w).

23. The pharmaceutical composition of any one of claims 1-19, wherein the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w).

24. The pharmaceutical composition of any one of claims 1-19, wherein the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w).

25. The pharmaceutical composition of any one of claims 1-24, wherein the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate.

26. The pharmaceutical composition of any one of claims 1-25, wherein the disintegrant comprises an intra-granular disintegrant and an extra-granular disintegrant.WSGR Docket No. 53238-724.60127. The pharmaceutical composition of any one of claims 1-26, wherein the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium.

28. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w).

29. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w).

30. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w).

31. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w).

32. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w).

33. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w).

34. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w).

35. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is about 1% (w / w).

36. The pharmaceutical composition of any one of claims 1-27, wherein the amount of the lubricant in the pharmaceutical composition is about 1.5% (w / w).

37. The pharmaceutical composition of any one of claims 1-36, wherein the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate.

38. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 25% (w / w) and about 35% (w / w).

39. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 26% (w / w) and about 34% (w / w).WSGR Docket No. 53238-724.60140. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 27% (w / w) and about 33% (w / w).

41. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 32% (w / w).

42. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 28% (w / w) and about 29% (w / w).

43. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 29% (w / w) and about 31% (w / w).

44. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 31% (w / w) and about 32% (w / w).

45. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 30% (w / w).

46. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 31% (w / w).

47. The pharmaceutical composition of any one of claims 1-37, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is about 32% (w / w).

48. The pharmaceutical composition of any one of claims 1-47, wherein the Compound 1 is in a free acid form.

49. The pharmaceutical composition of any one of claims 1-47, wherein the Compound 1 is in a salt form.

50. The pharmaceutical composition of claim 49, wherein the Compound 1 is a sodium salt.

51. The pharmaceutical composition of any one of the preceding claims, further comprising a coating layer.

52. The pharmaceutical composition of claim 51, wherein the coating layer comprises an Opadry coating film, an Eudragit coating film, or methacrylic acid copolymer.

53. The pharmaceutical composition of claim 51 or 52, wherein the coating layer comprises polyvinyl alcohol, Talc, calcium carbonate, and / or sodium lauryl sulfate.

54. The pharmaceutical composition of any one of claims 51-53, wherein the coating layer is about 1% (w / w) to about 10% (w / w) in the pharmaceutical composition.WSGR Docket No. 53238-724.60155. The pharmaceutical composition of any one of claims 51-53, wherein the coating layer is about 2% (w / w) to about 8% (w / w) in the pharmaceutical composition.

56. The pharmaceutical composition of any one of claims 51-53, wherein the coating layer is about 3% (w / w) to about 7% (w / w) in the pharmaceutical composition.

57. The pharmaceutical composition of any one of claims 51-53, wherein the coating layer is about 4% (w / w) to about 6% (w / w) in the pharmaceutical composition.

58. The pharmaceutical composition of any one of claims 51-53, wherein the coating layer is about 3% (w / w) to about 4% (w / w) in the pharmaceutical composition.

59. The pharmaceutical composition of any one of claims 1-58, comprising:(a) about 31% (w / w) of the Compound 1;(b) about 59% (w / w) of silicified microcrystalline cellulose;(c) about 9% (w / w) to about 10% (w / w) of croscarmellose sodium; and (d) about 0.5% (w / w) of magnesium stearate.

60. The pharmaceutical composition of any one of claims 1-58, comprising:(a) about 30% (w / w) of the Compound 1;(b) about 31% (w / w) of mannitol;(c) about 28% (w / w) of silicified microcrystalline cellulose;(d) about 10% (w / w) of croscarmellose sodium; and(e) about 1% (w / w) of magnesium stearate.

61. The pharmaceutical composition of any one of claims 1-58, comprising:(a) about 28% (w / w) to about 29% (w / w) of the Compound 1;(b) about 29% (w / w) to about 30% (w / w) of mannitol;(c) about 26% (w / w) to about 27% (w / w) of silicified microcrystalline cellulose; (d) about 9% (w / w) to about 10% (w / w) of croscarmellose sodium;(e) about 0.9% (w / w) to about 1% (w / w) of magnesium stearate; and(f) about 3% (w / w) to about 4% (w / w) of the coating layer.

62. The pharmaceutical composition of any one of claims 1-58, comprising:(a) about 31% (w / w) to about 32% (w / w) of the Compound 1;(b) about 29% (w / w) to about 30% (w / w) of mannitol;(c) about 28% (w / w) of silicified microcrystalline cellulose;(d) about 10% (w / w) of croscarmellose sodium; and(e) about 1.5% (w / w) of magnesium stearate.

63. The pharmaceutical composition of any one of claims 1-58, comprising:(a) about 28% (w / w) to about 29% (w / w) of the Compound 1;(b) about 27% (w / w) to about 28% (w / w) of mannitol;(c) about 25% (w / w) to about 26% (w / w) of silicified microcrystalline cellulose; (d) about 9% (w / w) to about 10% (w / w) of croscarmellose sodium;WSGR Docket No. 53238-724.601(e) about 1% (w / w) to about 1.5% (w / w) of magnesium stearate; and(f) about 7% (w / w) to about 8% (w / w) of the coating layer.

64. The pharmaceutical composition of any one of preceding claims, wherein the pharmaceutical composition is a tablet or in a capsule.

65. The pharmaceutical composition of any one of preceding claims, wherein the pharmaceutical composition is in a capsule.

66. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition is in a capsule comprising hydroxypropyl methylcellulose (HPMC).

67. The pharmaceutical composition of any one of claims 64-66, wherein the capsule comprises about 25 mg or 100 mg of the Compound 1 in a free acid form or a molar equivalent thereof.

68. The pharmaceutical composition of claim 64, wherein the pharmaceutical composition is a tablet.

69. The pharmaceutical composition of claim 68, wherein the pharmaceutical composition is a tablet that is produced through direct compaction.

70. The pharmaceutical composition of claim 68, wherein the pharmaceutical composition is a tablet that is produced through roller compaction.

71. The pharmaceutical composition of any one of claims 64 and 68-70, wherein the tablet comprises about 300 mg or 600 mg of the Compound 1 in a free acid form or a molar equivalent thereof.

72. The pharmaceutical composition of any one of claims 64 and 68-70, wherein the tablet comprises about 200 mg of the Compound 1 in a free acid form or a molar equivalent thereof.

73. The pharmaceutical composition of any one of claims 64 and 68-72, wherein the tablet is about 500 mg to about 1200 mg.

74. The pharmaceutical composition of any one of claims 64 and 68-70, wherein the tablet is about 700 mg to about 750 mg.

75. The pharmaceutical composition of any one of claims 64 and 68-70, wherein the tablet is about 1000 mg to about 1100 mg.

76. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition is administered orally.

77. A pharmaceutical composition comprising:(a) about 50% (w / w) to about 70% (w / w) 2-(3’-(3-(l-(4-(tert-butyl)benzyl)-4-ethyl-5- oxo-4,5-dihydro-lH-l,2,4-triazol-3-yl)propyl)-4-ethoxy-[l, 1’ -biphenyl] -3 -yl)acetic acid:WSGR Docket No. 53238-724.601thereof;(b) about 15% (w / w) to about 35% (w / w) of a diluent;(c) about 5% (w / w) to about 15% (w / w) of a disintegrant; and(d) about 0.1% (w / w) to about 2% (w / w) of a lubricant.

78. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 16% (w / w) and about 34% (w / w).

79. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 17% (w / w) and about 33% (w / w).

80. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 18% (w / w) and about 32% (w / w).

81. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 19% (w / w) and about 31% (w / w).

82. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 20% (w / w) and about 30% (w / w).

83. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 21% (w / w) and about 29% (w / w).

84. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 22% (w / w) and about 28% (w / w).

85. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 23% (w / w) and about 27% (w / w).

86. The pharmaceutical composition of claim 77, wherein the amount of the diluent in the pharmaceutical composition is between about 24% (w / w) and about 26% (w / w).

87. The pharmaceutical composition of any one of claims 77-86, wherein the diluent comprises a first diluent and a second diluent.

88. The pharmaceutical composition of any one of claims 77-87, wherein the amount of the first or second diluent in the pharmaceutical composition is between about 5% (w / w) and about 15% (w / w).

89. The pharmaceutical composition of any one of claims 77-87, wherein the amount of the first or second diluent in the pharmaceutical composition is between about 10% (w / w) and about 15% (w / w).WSGR Docket No. 53238-724.60190. The pharmaceutical composition of any one of claims 87-89, wherein the first diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate.

91. The pharmaceutical composition of any one of claims 87-90, wherein the second diluent comprises mannitol, microcrystalline cellulose, lactose, Starch 1500 Partially, pregelatinized maize starch, calcium carbonate, sorbitol, maltodextrin, or DiCalcium phosphate.

92. The pharmaceutical composition of any one of claims 87-91, wherein the second diluent comprises silicified microcrystalline cellulose.

93. The pharmaceutical composition of any one of claims 87-92, wherein first diluent comprises mannitol and the second diluent comprises silicified microcrystalline cellulose.

94. The pharmaceutical composition of any one of claims 77-93, wherein the diluent comprises an intra-granular diluent and an extra-granular diluent.

95. The pharmaceutical composition of any one of claims 77-94, wherein the diluent comprises intra-granular silicified microcrystalline cellulose and extra-granular silicified microcrystalline cellulose.

96. The pharmaceutical composition of any one of claims 77-95, wherein the amount of the disintegrant in the pharmaceutical composition is between about 6% (w / w) and about 14% (w / w).

97. The pharmaceutical composition of any one of claims 77-95, wherein the amount of the disintegrant in the pharmaceutical composition is between about 7% (w / w) and about 13% (w / w).

98. The pharmaceutical composition of any one of claims 77-95, wherein the amount of the disintegrant in the pharmaceutical composition is between about 8% (w / w) and about 12% (w / w).

99. The pharmaceutical composition of any one of claims 77-95, wherein the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 11% (w / w).

100. The pharmaceutical composition of any one of claims 77-95, wherein the amount of the disintegrant in the pharmaceutical composition is between about 9% (w / w) and about 10% (w / w).

101. The pharmaceutical composition of any one of claims 77-95, wherein the amount of the disintegrant in the pharmaceutical composition is about 10% (w / w).

102. The pharmaceutical composition of any one of claims 77-101, wherein the disintegrant comprises croscarmellose sodium, crospovidone, or sodium starch glycolate.

103. The pharmaceutical composition of any one of claims 77-101, wherein the disintegrant comprises an intra-granular disintegrant and an extra-granular disintegrant.WSGR Docket No. 53238-724.601104. The pharmaceutical composition of any one of claims 77-101, wherein the disintegrant comprises intra-granular croscarmellose sodium and extra-granular croscarmellose sodium.

105. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.8% (w / w).

106. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.2% (w / w) and about 1.4% (w / w).

107. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.3% (w / w) and about 1.3% (w / w).

108. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.4% (w / w) and about 1.2% (w / w).

109. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.5% (w / w) and about 1.1% (w / w).

110. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.6% (w / w) and about 1.0% (w / w).

111. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is between about 0.7% (w / w) and about 0.9% (w / w).

112. The pharmaceutical composition of any one of claims 77-104, wherein the amount of the lubricant in the pharmaceutical composition is about 1% (w / w).

113. The pharmaceutical composition of any one of claims 77-112, wherein the lubricant comprises magnesium stearate, calcium stearate, stearic acid, or sodium stearyl fumarate.

114. The pharmaceutical composition of any one of claims 77-113, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 52% (w / w) and about 68% (w / w).

115. The pharmaceutical composition of any one of claims 77-113, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 54% (w / w) and about 66% (w / w).

116. The pharmaceutical composition of any one of claims 77-113, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 56% (w / w) and about 64% (w / w).WSGR Docket No. 53238-724.601117. The pharmaceutical composition of any one of claims 77-113, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 58% (w / w) and about 62% (w / w).

118. The pharmaceutical composition of any one of claims 77-113, wherein the amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the pharmaceutical composition is between about 62% (w / w) and about 63% (w / w).

119. The pharmaceutical composition of any one of claims 77-118, wherein the Compound 1 is in a free acid form.

120. The pharmaceutical composition of any one of claims 77-118, wherein the Compound 1 is in a salt form.

121. The pharmaceutical composition of any one of claims 77-118, wherein the Compound 1 is a sodium salt.

122. The pharmaceutical composition of any one of claims 77-121, comprising:(a) about 62% (w / w) to about 63% (w / w) of the Compound 1;(b) about 13% (w / w) to about 14% (w / w) of mannitol;(c) about 12% (w / w) to about 13% (w / w) of silicified microcrystalline cellulose;(d) about 10% (w / w) of croscarmellose sodium; and(e) about 1% (w / w) of magnesium stearate.

123. The pharmaceutical composition of any one of claims 77-122, wherein the pharmaceutical composition is a tablet.

124. The pharmaceutical composition of any one of claims 77-122, wherein the pharmaceutical composition is a tablet that is produced through roller compaction.

125. The pharmaceutical composition of claim 123 or 124, wherein the tablet comprises about 300 mg to about 350 mg of the Compound 1 in a free acid form or a molar equivalent thereof.

126. The pharmaceutical composition of claim 123 or 124, wherein the tablet comprises about 600 mg to about 650 mg of the Compound 1 in a free acid form or a molar equivalent thereof.

127. The pharmaceutical composition of any one of claims 123-126, wherein the tablet is about 500 mg to about 1000 mg.

128. The pharmaceutical composition of any one of claims 123-126, wherein the tablet is about 500 mg.

129. The pharmaceutical composition of any one of claims 123-126, wherein the tablet is about 1000 mg.

130. The pharmaceutical composition of any one of claims 77-129, wherein the pharmaceutical composition is administered orally.

131. The pharmaceutical composition of any one of claims 68-75 and 123-129, wherein the tablet comprises a colorant.

132. The pharmaceutical composition of claim 131, wherein the colorant comprises a pigment.WSGR Docket No. 53238-724.601133. The pharmaceutical composition of any one of claims 68-75 and 123-132, wherein the tablet comprises an embossed surface.

134. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of any one of claims 1-133.

135. The method of claim 131, wherein the cancer comprises hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), renal cell carcinoma (RCC), colorectal cancer (CRC), pancreatic cancer (PANC), prostate cancer, non-small cell lung cancer (NSCLC), or metastatic castration -resistant prostate cancer (mCRPC).

136. The method of claim 134 or 135, further comprising administering to the subject a second therapy.

137. The method of any one of claims 134-136, wherein the administering comprises administering orally.

138. The method of any one of claims 134-137, wherein the administering comprises administering orally a granule of the pharmaceutical composition, wherein a dispenser comprising a pouch or sachet contains the granule of the pharmaceutical composition.

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