TECHNICAL FIELD

The present invention provides derivatives of aminopyrazine compounds that modulate the activity of phosphoinositide 3-kinases-gamma (RI3Kg) and are useful in the treatment of diseases related to the activity of RI3Kg including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.

BACKGROUND

The phosphoinositide 3-kinases (PI3Ks) belong to a large family of lipid signaling kinases that phosphorylate phosphoinositides at the D3 position of the inositol ring (Cantley, Science, 2002, 296(5573): 1655-7). PI3Ks are divided into three classes (class I, II, and III) according to their structure, regulation and substrate specificity. Class I PI3Ks, which include RI3Ka, RI3Kb, RI3Kg, and PI3K8, are a family of dual specificity lipid and protein kinases that catalyze the phosphorylation of phosphatidylinosito-4,5-bisphosphate (PIP 2) giving rise to phosphatidylinosito-3,4,5-trisphosphate (PIP3). PIP3 functions as a second messenger that controls a number of cellular processes, including growth, survival, adhesion and migration. All four class I PI3K isoforms exist as heterodimers composed of a catalytic subunit (pi 10) and a tightly associated regulatory subunit that controls their expression, activation, and subcellular localization. RI3Ka, RI3Kb, and PI3K6 associate with a regulatory subunit known as p85 and are activated by growth factors and cytokines through a tyrosine kinase- dependent mechanism (Jimenez, et al., J Biol Chem., 2002, 277(44):41556-62) whereas RI3Kg associates with two regulatory subunits (plOl and p84) and its activation is driven by the activation of G-protein-coupled receptors (Brock, et al., J Cell Biol., 2003, 160(l):89-99). PI3Koc and RI3Kb are ubiquitously expressed. In contrast, RI3Kg and PI3K8 are predominantly expressed in leukocytes (Vanhaesebroeck, et al., Trends Biochem Sci., 2005, 30(4): 194-204).

Expression of RI3Kg is mainly restricted to hematopoietic system, although it can be also detected at lower level in endothelium, heart and brain. RI3Kg knockout or kinase dead knock in mice are normal and fertile and do not present any overt adverse phenotypes.

Analysis at the cellular level indicates that RI3Kg is required for GPCR ligand-induced PtdINs (3,4,5)P3 production, chemotaxis and respiratory burst in neutrophils. RBKg-null macrophages and dendritic cell exhibit reduced migration towards various chemoattractants. T-cells deficient in RI3Kg show impaired cytokine production in response to anti-CD3 or Con A stimulation. RI3Kg working downstream of adenosine A3A receptor is critical for sustained degranulation of mast cells induced by FCsRI cross-linking with IgE. RI3Kg is also essential for survival of eosinophils (Ruckle et ak, Nat. Rev. Drug Discovery, 2006, 5, 903-918)

Given its unique expression pattern and cellular functions, the potential role of RI3Kg in various autoimmune and inflammatory disease models has been investigated with genetic and pharmacological tools. In asthma and allergy models, RI3Kg mice or mice treated with RI3Kg inhibitor showed a defective capacity to mount contact hypersensitivity and delayed- type hypersensitivity reactions. In these models, RI3Kg was shown to be important for recruitment of neutrophils and eosinopohils to airways and degranulation of mast cells (see e.g. Laffargue et ak, Immunity, 2002, 16, 441-451; Prete et ak, The EMBO Journal, 2004, 23, 3505-3515; Pinho et ak, L. Leukocyte Biology, 2005, 77, 800-810; Thomas et ak, Eur. J. Immunol. 2005, 35, 1283-1291; Doukas et al .../ Pharmacol. Exp Ther. 2009, 328, 758-765).

In two different acute pancreatitis models, genetic ablation of RI3Kg significantly reduced the extent of acinar cell injury /necrosis and neutrophil infiltration without any impact on secretive function of isolated pancreatic acini (Lupia et ak, Am. J. Pathology, 2004, 165, 2003-2011). RI3Kg mice were largely protected in four different models of rheumatoid arthritis (CIA, a-CII-IA, K/BxN serum transfer and TNF transgenic) and RI3Kg inhibition suppressed the progression of joint inflammation and damage in the CIA and oc-CII-IA models (see e.g., Camps et ak, Nat. Medicine, 2005, 11, 939-943; Randis et ak, Eur. J.

Immunol, 2008, 38, 1215-1224; Hayer et ak, FASB , 2009, 4288-4298). In the MKL-lpr mouse model of human systemic lupus erythematous, inhibition of RI3Kg reduced glomerulonephritis and prolonged life span (Barber et ak, Nat. Medicine, 2005, 9, 933-935).

There is evidence suggesting that chronic inflammation due to infiltration by myeloid-derived cells is a key component in the progression of neurodegeneration diseases, such as Alzheimer’s disease (AD) (Giri et ak, Am. J. Physiol. Cell Physiol., 2005, 289, C264- C276; El Khoury et ak, Nat. Med., 2007, 13, 432-438). In line with this suggestion, RI3Kg inhibition was shown to attenuate Ab( 1 -40)-induccd accumulation of activated astrocytes and microglia in the hippocampus and prevent the peptide-induced cognitive deficits and synaptic dysfunction in a mouse model of AD (Passos et ak, Brain Behav. Immun. 2010, 24, 493-501). RI3Kg deficiency or inhibition also was shown to delay onset and alleviate symptoms in experimental autoimmune encephalomyelitis in mice, a mouse model of human multiple sclerosis, which is another form of neurodegeneration disease (see e.g., Rodrigues et ak, J. Neuroimmunol. 2010, 222, 90-94; Berod et ak, Euro. J. Immunol. 2011, 41, 833-844;

Comerford et ak, PLOS one, 2012, 7, e45095; Li et ak, Neuroscience, 2013, 253, 89-99).

Chronic inflammation has been formally recognized as one of the hallmarks for many different types of cancers. Accordingly, selective anti-inflammatory drugs represent a novel class of anti-cancer therapies (Hanahan and Weinberg, Cell, 2011, 144, 646-674). Since RI3Kg is reported to mediate various inflammatory processes, its role as an immune oncology target has also been investigated. A recent study reported that RI3Kg deficiency suppressed tumor growth in the syngeneic models of lung cancer, pancreatic cancer and melanoma (LLC, PAN02 and B16). RI3Kg deficiency or inhibition also inhibited tumor growth in a spontaneous breast cancer model (Schmid et al., Cancer Cell, 2011, 19, 715-727). A further study reported that RI3Kg deficiency could ameliorate inflammation and tumor growth in mice having colitis-associated colon cancer, (Gonzalez-Garcia et al., Gastroenterology, 2010, 138, 1373-1384). Detailed mechanistic analysis indicates that tumor infiltration by CD1 lb ⁺ myeloid cells can cause protumorigenic inflammation at tumor sites and RI3Kg in the myeloid cells is critical in mediating signaling of various chemoattractants in bring the cells to the tumor (Schmid et al., Cancer Cell, 2011, 19, 715-727). Other studies suggest that RI3Kg is also required for differentiation of naive myeloid cells into M2 macrophages at tumor sites. M2 macrophages promote tumor growth and progression by secreting immunosuppressive factors such arginase 1, which depletes the tumor microenvironment of arginine, thereby promoting T-cell death and NK cell inhibition (Schmidt et al., Cancer Res. 2012, 72 (Suppl 1: Abstract, 411, Kaneda et al., Cancer Res., 74 (Suppl 19: Abstract 3650)).

In addition to its potential role in promoting protumorigenic microenvironment,

RI3Kg may play a direct role in cancer cells. RI3Kg is reported to be required for signaling from the Kaposi’s sarcoma-associated herpevirus encoded vGPCR oncogene and tumor growth in a mouse model of sarcoma (Martin et al., Cancer Cell, 2011, 19, 805-813). RI3Kg was also suggested to be required for growth of T-ALL (Subramanjam et al., Cancer Cell, 2012, 21, 459-472), PD AC and HCC cells (Falasca and Maffucci, Frontiers in Physiology, 2014, 5, 1-10). Moreover, in a survey of driver mutations in pancreatic cancer, RI3Kg gene was found to contain second highest scoring predicted driven mutation (R839C) among the set of genes not previously identified as a driver in pancreatic cancer (Carter et al., Cancer Biol. Ther. 2010, 10, 582-587).

Finally, RI3Kg deficiency also has been reported to offer protection to experimental animals in different cardiovascular disease models. For examples, lack of RI3Kg would reduce angiotensin-evoked smooth muscle contraction and, therefore, protect mice from angiotensin-induced hypertension (Vecchione et al., J. Exp. Med. 2005, 201, 1217-1228). In rigorous animal myocardial infarction models, RI3Kg inhibition provided potent

cardioprotection, reducing infarct development and preserving myocardial function (Doukas et al., Proc. Natl. Acad. Sci. USA, 2006, 103, 19866-19871). For these reasons, there is a need to develop new RI3Kg inhibitors that can be used for the treatment of diseases such as cancer, autoimmune disorders, and inflammatory and cardiac diseases. This application is directed to this need and others.

SUMMARY

The present invention relates to, inter alia, compounds of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein constituent members are defined herein.

The present invention further provides pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a

pharmaceutically acceptable carrier.

The present invention further provides methods of inhibiting an activity of RI3Kg kinase comprising contacting the kinase with a compound of Formula (I), or a

pharmaceutically acceptable salt thereof.

The present invention further provides methods of treating a disease or a disorder associated with abnormal RI3Kg kinase expression or activity in a patient by administering to said patient a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

The present invention further provides a compound of Formula (I), or a

pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

The present invention further provides use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein. DETAILED DESCRIPTION

Compound subset (A)

The present application provides, inter alia, compounds of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein:

X ¹ is N or CR ¹ ;

R ¹ is selected from H, D, halo, Ci-b alkyl, Ci-b alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, CN, OH and N¾;

R ² is a C1-6 haloalkyl, wherein each halogen is independently selected from F and Cl, wherein the haloalkyl is optionally substituted with C(0)NR ^a R ^b or 1, 2, 3 or 4 independently selected R ^M substituents;

each R ^M is independently selected from D, OH, NO ₂ , CN, halo, C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _1-3 haloalkyl, cyano-Ci- ₃ alkyl, HO-C _1-3 alkyl, C _1-3 alkoxy-Ci- ₃ alkyl, C _3-5 cycloalkyl, C _1-3 alkoxy, C _1-3 haloalkoxy, amino, C _1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C ₁ - ₃ alkylsulfmyl, C ₁ - ₃ alkylsulfonyl, carbamyl, C ₁ - ₃ alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C _1-3 alkylcarbonyl, C _1-4 alkoxycarbonyl, C _1-3 alkylcarbonylamino, C _1-3 alkoxycarbonylamino, C _1-3 alkylcarbonyloxy, aminocarbonyloxy, C _1-3

alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C _1-3 alkylsulfonylamino, aminosulfonyl, C ₁ - ₃ alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C _1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C _1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl) aminocarbonylamino;

R ³ is selected from H, D, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and N¾;

R ³ is selected from H, D, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and NH ₂ ;

or, alternatively, R ³ and R ³ together form an oxo group; R ⁴ , R ⁵ and R ⁶ are each independently selected from H, D, halo, CN, OH, N¾, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-b alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, cyano-Ci- ₆ alkyl, HO-C _I - ₆ alkyl, Ci-6 alkoxy-Ci- ₆ alkyl, C3-6 cycloalkyl, Ci-6 alkylamino, di(Ci-6 alkyl)amino, and C(0)NR ^a R ^b ;

each R ^a and R ^b is independently selected from H, Ci-b alkyl, Ci-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-Ci- ₆ alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered

heterocycloalkyl, phenyl-Ci- ₆ alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a and R ^b are each optionally substituted with 1, 2, 3 or 4 independently selected R ^M substituents;

R ⁷ is selected from C(0)R ^b7 , C(0)NR ^c7 R ^d7 , C(0)NR ^c7 (0R ^b7 ), C(0)OR ^a7 ,

each R ^a7 , R ^b7 , R ^c7 , and R ^d7 is independently selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl and 4-12 membered heterocycloalkyl, wherein the Ci- ₆ alkyl, C2- 6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl and 4-12 membered heterocycloalkyl of R ^a7 , R ^b7 , R ^c7 , and R ^d7 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7A substituents;

or, R ^c7 and R ^d7 , together with the N atom to which they are attached, form a 5- or 6- membered heteroaryl or a 4-14-membered heterocycloalkyl group, wherein the 5- or 6- membered heteroaryl or 4-14-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7A substituents;

each R ^e7 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYu aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-14 aryl-Ci- ₆ alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl-;

R ⁸ and R ⁹ are each independently selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, C(0)R ^b8 , alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ⁸ and R ⁹ are each optionally substituted with 1, 2, 3, or 4 independently selected R ^8A substituents;

or, R ⁸ and R ⁹ , together with the N atom to which they are attached, form a 5- or 6- membered heteroaryl, or a 4-10 membered heterocycloalkyl group, wherein the 5- or 6- membered heteroaryl, or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R ^8A substituents;

each R ^7A is independently selected from D, halo, Ci-b alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, N0 ₂ , OR ^a71 , SR ^a71 , NHOR ^a71 , C(0)R ^b71 , C(0)NR ^c71 R ^d71 ,

P(0)(0R ^h71 )(0R ^l71 ), and BR ^j71 R ^k71 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4- 10 membered heterocycloalkyl, of R ^7A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents; each R ^a71 , R ^b71 , R ^c71 , and R ^d71 is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a71 , R ^b71 , R ^c71 , and R ^d71 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

or, any R ^c71 and R ^d71 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^7B substituents; each R ^e71 is independently selected from H, OH, CN, Ci-b alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^m and R ^®71 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^h71 and R ^l71 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j71 and R ^k71 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j71 and R ^k71 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^7B is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a72 , SR ^a72 , NHOR ^a72 , C(0)R ^b72 , C(0)NR ^c72 R ^d72 , C(0)NR ^c72 (0R ^b72 ), C(0)0R ^a72 , 0C(0)R ^b72 ,

0C(0)NR ^c72 R ^d72 , NR ^c72 R ^d72 , NR ^c72 NR ^c72 R ^d72 , NR ^c72 C(0)R ^b72 , NR ^c72 C(0)0R ^a72 ,

NR ^c72 C(0)NR ^c72 R ^d72 , C(=NR ^e72 )R ^b72 , C(=NOH)R ^b72 , C(=NCN)R ^b72 , C(=NR ^e72 )NR ^c72 R ^d72 , NR ^c72 C(=NR ^e72 )NR ^c72 R ^d72 , NR ^c72 C(=NR ^e72 )R ^b72 , NR ^c72 C(=NOH)NR ^c72 R ^d72 ,

NR ^c72 C(=NCN)NR ^c72 R ^d72 , NR ^c72 S(0)R ^b72 , NR ^c72 S(0)NR ^c72 R ^d72 , NR ^c72 S(0) ₂ R ^b72 ,

NR ^c72 S(0) ₂ NR ^c72 R ^d72 , S(0)R ^b72 , S(0)NR ^c72 R ^d72 , S(0) ₂ R ^b72 , S(0) ₂ NR ^c72 R ^d72 ,

0S(0)(=NR ^e72 )R ^b72 , 0S(0) ₂ R ^b72 , SF ₅ , P(0)R ^f72 R ^g72 , 0P(0)(0R ^h72 )(0R ^l72 ),

P(0)(0R ^h72 )(0R ^l72 ), and BR ^j72 R ^k72 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^7B are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents; each R ^a72 , R ^b72 , R ^c72 , and R ^d72 is independently selected from H, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a72 , R ^b72 , R ^c72 , and R ^d72 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

or, any R ^c72 and R ^d72 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

each R ^e72 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^{1 2} and R ^®72 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci-6haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h72 and R ¹⁷² is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j72 and R ^k72 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j72 and R ^k72 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^7C is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a73 , SR ^a73 ,

P(0)(0R ^h73 )(0R ^l73 ), and BR ^j73 R ^k73 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- C1-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^7C are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

each R ^a73 , R ^b73 , R ^c73 , and R ^d73 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl -C 1-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a73 , R ^b73 , R ^c73 , and R ^d73 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

or, any R ^c73 and R ^d73 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^7D substituents;

each R ^e73 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^{1 3} and R ^®73 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h73 and R ^l73 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j73 and R ^k73 is independently selected from OH, Ci- ₆ alkoxy, and C1-6 haloalkoxy;

or any R ^j73 and R ^k73 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and Ci- ₆ haloalkyl; each R ^7D is independently selected from H, D, halo, CN, NO2, SF5, Ci-b alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl;

each R ^a8 , R ^b8 , R ^c8 , and R ^d8 is independently selected from H, Ci- ₆ alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a8 , R ^b8 , R ^c8 , and R ^d8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

or, any R ^c8 and R ^d8 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

each R ^e8 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-; each R ^8A is independently selected from D, halo, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ³⁸¹ , SR ³⁸¹ ,

P(0)(0R ^h81 )(0R ¹⁸¹ ), and BR ^j81 R ^k81 , wherein the C _M alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₆ -io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- C1-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl) -C 1-6 alkyl- of R ^8A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

each R ^a81 , R ^b81 , R ^c81 , and R ^d81 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a81 , R ^b81 , R ^c81 , and R ^d81 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

or, any R ^c81 and R ^d81 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

each R ^e81 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-; each R and R ^®81 is independently selected from H, Ci- ₆ alkyl, Ci-6 alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h81 and R ^l81 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j81 and R ^k81 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j81 and R ^k81 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; and each R ^8B is independently selected from H, D, halo, CN, NO2, SR. Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C 3 -7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl.

In some embodiments, either: (a) R ³ and R ³ together form an oxo group; or (b) R ⁸ is C(0)R ^b8 .

In some embodiments, X ¹ is N.

In some embodiments, X ¹ is CR ¹ .

In some embodiments, R ¹ is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ¹ is selected from H, D, and methyl.

In some embodiments, R ¹ is H.

In some embodiments, R ² is a Ci- ₆ haloalkyl, wherein each halogen of the Ci- ₆ haloalkyl is independently selected from F and Cl.

In some embodiments, R ² is a C _1-3 haloalkyl, wherein each halogen of the C _1-3 haloalkyl is independently selected from F and Cl.

In some embodiments, R ² is selected from CF ₃ , CCI ₃ , CF ₂ H, CCfrH, CF ₂ R ^M , CCl ₂ R ^M , CFH ₂ , CCIH ₂ , CFHR ^m , CC1HR ^m , CF(R ^m ) ₂ and CC1(R ^M ) ₂ .

In some embodiments, R ² is selected from CF ₃ , CF ₂ H, CF ₂ R ^M , CFH ₂ , CFHR ^M , and CF(R ^m ) ₂ .

In some embodiments, R ^M is selected from D, halo, C _1-3 alkyl, and C _1-3 haloalkyl.

In some embodiments, R ^M is selected from halo and C _1-3 haloalkyl. In some embodiments, R ² is Ci-b haloalkyl, wherein each halogen is F.

In some embodiments, R ² is Ci- ₆ haloalkyl, wherein each halogen is Cl.

In some embodiments, R ² is selected from CH ₂ F, CHF ₂ , CF ₃ , and CF ₂ CF ₃ .

In some embodiments, R ² is CF ₃ or CHF ₂ .

In some embodiments, R ² is CF ₃ .

In some embodiments, R ² is CH ₂ F.

In some embodiments, R ² is CHF ₂ .

In some embodiments, R ² is CF ₂ CF ₃ .

In some embodiments, R ³ is selected from H, D, Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, and NH ₂ .

In some embodiments, R ³ selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ³ is H or D.

In some embodiments, R ³ is H.

In some embodiments, R ³ is selected from H, D, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and NH ₂ .

In some embodiments, R ³ is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ³ is H or D.

In some embodiments, R ³ is H.

In some embodiments, R ³ and R ³ together form an oxo group.

In some embodiments, R ⁴ is selected from H, D, halo, Ci- ₆ alkyl, Ci- ₆ alkoxy, C _2-6 alkenyl, C ₂ - ₆ alkynyl, Ci-6 haloalkyl, Ci-6haloalkoxy, CN, OH, and NH ₂ , wherein the Ci- ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁴ is selected from H, D, halo, CN, OH, NH ₂ , and Ci- ₆ alkyl.

In some embodiments, R ⁴ is selected from H, D, and Ci- ₆ alkyl, wherein the Ci- ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁴ is H.

In some embodiments, R ⁴ is D.

In some embodiments, R ⁵ is selected from H, D, halo, Ci- ₆ alkyl, Ci- ₆ alkoxy, C _2-6 alkenyl, C ₂ - ₆ alkynyl, Ci-6 haloalkyl, Ci-6haloalkoxy, CN, OH, and NH ₂ , wherein the Ci- ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁵ is selected from H, D, halo, CN, OH, NH ₂ , and Ci- ₆ alkyl.

In some embodiments, R ⁵ is selected from H, D, and Ci- ₆ alkyl, wherein the Ci- ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁵ is H.

In some embodiments, R ⁵ is D. In some embodiments, R ³ and R ⁴ are each H.

In some embodiments, R ³ and R ⁵ are each H.

In some embodiments, R ⁴ and R ⁵ are each H.

In some embodiments, R ³ , R ³ , R ⁴ , and R ⁵ are each H.

In some embodiments, R ³ and R ³ together form an oxo group; and R ⁴ and R ⁵ are each H.

In some embodiments, R ⁶ is selected from H, D, halo, Ci- ₆ alkyl, Ci-b alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, Ci- ₆ haloalkoxy, CN, OH, and NH ₂ , wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁶ is selected from H, D, and Ci- ₆ alkyl, wherein the Ci- ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁶ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl.

In some embodiments, R ⁶ is Ci-b alkyl.

In some embodiments, R ⁶ is methyl.

In some embodiments, R ⁶ is CD ₃ .

In some embodiments, R ⁶ is H.

In some embodiments, R ⁶ is D.

In some embodiments, R ⁷ is selected from C(0)R ^b7 , C(0)NR ^c7 R ^d7 , C(0)NR ^c7 (0R ^b7 ),

each R ^a7 , R ^b7 , R ^c7 , and R ^d7 is independently selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl and 4-10 membered heterocycloalkyl, wherein the Ci- ₆ alkyl, C2- 6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl and 4-10 membered heterocycloalkyl of R ^a7 , R ^b7 , R ^c7 , and R ^d7 are each optionally substituted with 1, 2, or 3 independently selected R ^7A substituents; or, R ^c7 and R ^d7 , together with the N atom to which they are attached, form a 5- or 6- membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, or 3 independently selected R ^7A substituents; and

each R ^e7 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-.

In some embodiments, R ⁷ is C(0)NR ^c7 R ^d7 . In some embodiments, R ^c7 is selected from H, Ci-b alkyl, C2-6 alkenyl, and C2-6 alkynyl.

In some embodiments, R ^c7 is H.

In some embodiments, R ^d7 is selected from H, Ci-b alkyl, C3-10 cycloalkyl, and 4-8 membered heterocycloalkyl, wherein the Ci- ₆ alkyl, C3-10 cycloalkyl and 4-8 membered heterocycloalkyl of R ^d7 are each optionally substituted with 1 or 2 independently selected R ^7A substituents.

In some embodiments, each R ^7A is independently selected from D, halo, Ci-b alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR ^a71 , and SR ^a71 , wherein the Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl are each optionally substituted by 1 or 2 independently selected R ^7B substituents.

In some embodiments, each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-8 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR ^a71 , and SR ^a71 .

In some embodiments, each R ^7A is independently selected from D, halo, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-8 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR ^a71 , and SR ^a71 ; and

each R ^a71 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

In some embodiments, each R ^7A is independently selected from halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C3-8 cycloalkyl, CN, and OR ^a71 .

In some embodiments, each R ^7A is independently selected from halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C3-8 cycloalkyl, CN, and OR ^a71 , wherein each R ^a71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, each R ^7B is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, CN, OR ^a72 , wherein the Ci-b alkyl is optionally substituted by 1 or 2 OH groups.

In some embodiments, each R ^7B is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, CN, OR ^a72 , wherein the Ci-b alkyl is optionally substituted by 1 or 2 OH groups; and

each OR ^a72 is independently selected from H and Ci- ₆ alkyl. In some embodiments, R ^d7 is selected from Ci-b alkyl, hydroxyl-Ci- ₆ alkyl, cyano-Ci- ₆ alkyl, monocyclic C3-6 cycloalkyl, bicyclic C5-8 cycloalkyl, monocyclic 4-6 membered heterocycloalkyl, and bicyclic 4-10 membered heterocycloalkyl wherein the Ci- ₆ alkyl, hydroxyl -C1-6 alkyl, cyano-Ci- ₆ alkyl, monocyclic C3-6 cycloalkyl, bicyclic C5-8 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted by 1 or 2 R ^7A substituents independently selected from halo, OH, CN, C1-3 alkoxy, C1-3 haloalkyl, 4-10 membered heterocycloalkyl, and C3-10 cycloalkyl.

In some embodiments, R ^d7 is selected from Ci- ₆ alkyl, hydroxyl-Ci- ₆ alkyl, cyano-Ci- ₆ alkyl, monocyclic C3-6 cycloalkyl, bicyclic C5-8 cycloalkyl, and 4-6 membered

heterocycloalkyl, wherein the Ci- ₆ alkyl, hydroxyl-Ci- ₆ alkyl, cyano-Ci- ₆ alkyl, monocyclic C3- ₆ cycloalkyl, bicyclic C cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted by 1 or 2 R ^7A substituents independently selected from halo, OH, CN, C1-3 alkoxy, and C3-10 cycloalkyl.

In some embodiments, R ^d7 is selected from ethyl, 2-cyanoethyl, 2,2,2-trifluoroethyl,

2-propyl, l-(cyanomethyl)propyl, 2-methoxy-2-methylpropyl, 2-cyano-2,2-dimethylethyl, 2- hydroxy-2-methylprop-l-yl, 2-cyano-l-methylethyl, 2 -hydroxy- 1-methylethyl, 2 -hydroxy - 1,1-dimethylethyl, 1-cyanocycloprop-l-ylethyl, 1-cyanocyclobut-l-ylethyl, 4- hydroxycyclohexyl, 4-methoxycyclohexyl, 4-hydroxy-4-methylcyclohexyl, 4-hydroxy-4- (trifluoromethyl) cyclohexyl, 4-(l-hydroxy-l-methylethyl)cyclohexyl, 4,4-difluorocyclohexyl,

3-cyanobicyclo[l.1. l]pentan-l-yl, 4-cyanobicyclo[2. l.l]hexan-l-yl, 4- cyanobicyclo[2.2.2]octan-l-yl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, 7- oxabicyclo[2.2. l]heptan-2-yl, 2-(tetrahydrofuran-3-yl) ethyl, 3,3,3-trifluoro-2-hydroxypropyl and tetrahydropyran-4-yl.

In some embodiments, R ^d7 is selected from ethyl, 2-cyanoethyl, 2,2,2-trifluoroethyl,

2-propyl, l-(cyanomethyl)propyl, 2-methoxy-2-methylpropyl, 2-cyano-2,2-dimethylethyl, 2- hydroxy-2-methylprop-l-yl, 2-cyano-l-methylethyl, 2-hydroxy- 1-methylethyl, 2 -hydroxy - 1,1-dimethylethyl, 1-cyanocycloprop-l-ylethyl, 1-cyanocyclobut-l-ylethyl, 4- hydroxycyclohexyl, 4-methoxycyclohexyl, 4-hydroxy-4-methylcyclohexyl, 4-hydroxy-4- (trifluoromethyl) cyclohexyl, 4-(l-hydroxy-l-methylethyl)cyclohexyl, 4,4-difluorocyclohexyl,

3-cyanobicyclo[l.1. l]pentan-l-yl, 4-cyanobicyclo[2. l.l]hexan-l-yl, 4- cyanobicyclo[2.2.2]octan-l-yl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, and

tetrahydropyran-4-yl.

In some embodiments, R ^c7 and R ^d7 , together with the N atom to which they are attached, form an azetidine ring, optionally substituted with 1, 2, or 3 independently selected R ^7A substituents. In some embodiments, R ^c7 and R ^d7 , together with the N atom to which they are attached, form an azetidine ring, optionally substituted with 1, 2, or 3 independently selected R ^7A substituents selected from methyl and methoxymethyl.

In some embodiments, R ^c7 and R ^d7 , together with the N atom to which they are attached, form a group selected from 2-(methoxymethyl)azetidin-l-yl and 2,2- dimethylazetidin-1 -yl.

In some embodiments, R ^c7 and R ^d7 , together with the N atom to which they are attached, form a 2,3-dihydro-lH-pyrrolo[2,3-b]pyridin-l-yl group.

In some embodiments, R ⁸ is selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, C3-10 cycloalkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C3-10 cycloalkyl.

In some embodiments, R ⁸ is selected from H, Ci-b alkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is H or Ci-b alkyl.

In some embodiments, R ⁸ is H, methyl, ethyl, propyl or isopropyl.

In some embodiments, R ⁸ is H or C(0)R ^b8 .

In some embodiments, R ⁸ is H.

In some embodiments, R ⁸ is C(0)R ^b8 .

In some embodiments, R ^b8 is selected from H, Ci-b alkyl, Ci-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci-b alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents.

In some embodiments, R ^b8 is selected from H, Ci-b alkyl, and Ci-b haloalkyl, wherein the Ci- ₆ alkyl of R ^b8 is optionally substituted with 1 or 2 R ^8A substituents independently selected from D, halo, CN, NO2, OH, and SH.

In some embodiments, R ^b8 is selected from methyl, fluoromethyl, cyanomethyl, and hydroxypropyl.

In some embodiments, R ^b8 is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ^b8 is selected from H, D, and methyl.

In some embodiments, R ^b8 is H.

In some embodiments, R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- 6 haloalkyl and C3-10 cycloalkyl.

In some embodiments, R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci- ₆ haloalkyl. In some embodiments, R ⁹ is H or Ci-b alkyl.

In some embodiments, R ⁹ is selected from H, methyl, ethyl, propyl, and isopropyl.

In some embodiments, R ⁹ is H.

In some embodiments, R ⁸ and R ⁹ are each H.

In some embodiments:

R ³ is selected from H, D, Ci-b alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci-b haloalkyl, and

NH ₂ ;

R ³ is selected from H, D, Ci-b alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci-b haloalkyl, and NH2; and

R ⁸ is C(0)R ^b8 .

In some embodiments:

R ³ and R ³ together form an oxo group; and

R ⁸ is selected from H, Ci-b alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, Ci-b haloalkyl, and C ₃ -7 cycloalkyl.

In some embodiments:

X ¹ is N or CH;

R ² is a Ci-6 haloalkyl, wherein each halogen of the Ci- ₆ haloalkyl is independently selected from F and Cl;

R ³ is selected from H, D, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, and

NH ₂ ;

R ³ is selected from H, D, Ci-b alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, Ci- ₆ haloalkyl, and

NH ₂ ;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁵ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁶ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁷ is C(0)NR ^c7 R ^d7 ;

R ^c7 and R ^d7 are each independently selected H, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and 4-8 membered heterocycloalkyl, wherein the Ci-b alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, C _3-10 cycloalkyl, and 4-8 membered heterocycloalkyl of R ^c7 and R ^d7 are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

R ⁸ is selected from H, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, and C(0)R ^b8 ;

R ⁹ is selected from H, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and Ci- ₆ haloalkyl; each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-8 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR ^a71 , and SR ^a71 ;

each R ^a71 is independently selected from H, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents; and

each R ^8A is independently selected from D, halo, CN, NO2, OH, and SH.

In some embodiments:

X ¹ is N or CH;

R ² is a C1-3 haloalkyl, wherein each halogen of the C 1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is selected from H and Ci-b alkyl;

R ⁵ is selected from H and Ci- ₆ alkyl;

R ⁶ is selected from H and Ci- ₆ alkyl;

R ⁷ is C(0)NR ^c7 R ^d7 ;

R ^c7 is selected from H, Ci-b alkyl, C2-6 alkenyl, and C2-6 alkynyl;

R ^d7 is selected from H, Ci- ₆ alkyl, C 3-10 cycloalkyl, and 4-8 membered

heterocycloalkyl, wherein the Ci- ₆ alkyl, C3-10 cycloalkyl and 4-8 membered heterocycloalkyl of R ^d7 are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H;

each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-8 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR ^a71 , and SR ^a71 ;

each R ^a71 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci-b alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents; and

each R ^8A is independently selected from D, halo, CN, NO2, OH, and SH. In some embodiments:

X ¹ is N or CH;

R ² is a Ci- ₃ haloalkyl, wherein each halogen of the C 1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is H;

R ⁵ is H;

R ⁶ is C1-6 alkyl;

R ⁷ is C(0)NR ^c7 R ^d7 ;

R ^c7 is selected from H and C1-6 alkyl;

R ^d7 is selected from H, C 1-6 alkyl, C3 -10 cycloalkyl, and 4-8 membered

heterocycloalkyl, wherein the C1-6 alkyl, C3-10 cycloalkyl and 4-8 membered heterocycloalkyl of R ^d7 are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H;

each R ^7A is independently selected from halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C3-8 cycloalkyl, CN, OR ^a71 ;

each R ^a71 is independently selected from H and Ci- ₆ alkyl; and

R ^b8 is selected from H, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

In some embodiments, the compound of Formula (I) is a compound of Formula (II):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula (III):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (IV):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula

(IVa):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula (V):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (VI):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (VII):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula

(Vila):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula

(VIII):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (IX):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound is selected from:

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(2-hydroxy-2-methylpropyl)pyrazine-2-carboxa mide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(tetrahydro-2H-pyran-4-yl)pyrazine-2-carboxa mide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((lr,4r)-4-hydroxycyclohexyl)pyrazine-2-carb oxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((l-cyanocyclopropyl)methyl)pyrazine-2-carbo xamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-isopropylpyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(4,4-dilluorocyclohexyl)pyrazine-2-carboxami de;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-ethylpyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((S)-l-cyanopropan-2-yl)pyrazine-2 -carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((R)-tetrahydro-2H-pyran-3-yl)pyrazine-2-car boxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((S)-tetrahydro-2H-pyran-3-yl)pyrazine-2-car boxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((S)-tetrahydroluran-3-yl)pyrazine-2-carboxa mide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl) -N-((S)- 1 -hydroxypropan-2-yl)pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(l-hydroxy-2-methylpropan-2-yl)pyrazine-2-ca rboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(2-cyanoethyl)pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(2-cyano-2-methylpropyl)pyrazine-2-carboxami de;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((l-cyanocyclobutyl)methyl)pyrazine-2-carbox amide; 3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((lr,4r)-4-hydroxy-4-methylcyclohexyl)pyrazi ne-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((lr,4r)-4-hydroxy-4-(trifluoromethyl)cycloh exyl)pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((lr,4r)-4-(2-hydroxypropan-2-yl)cyclohexyl) pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl) -N-((S)- 1 -cyanobutan-2-yl)pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(2-methoxy-2-methylpropyl)pyrazine-2-carboxa mide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-((lr,4r)-4-methoxycyclohexyl)pyrazine-2-carb oxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl) -N-(3-cyanobicyclo[l .1. l]pentan-l -yl)pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl) -N-(4-cyanobicyclo[2.1. l]hexan-l -yl)pyrazine-2-carboxamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(4-cyanobicyclo[2.2.2]octan-l-yl)pyrazine-2- carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- l-oxopropan-2-yl)-2-methylphenyl)- N-methylpyrazine-2-carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- l-oxopropan-2-yl)-2-methylphenyl)- N-ethylpyrazine-2-carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- 1 -oxopropan-2-yl)-2 -methylphenyl)- N-((l-cyanocyclopropyl)methyl)pyrazine-2 -carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- 1 -oxopropan-2-yl)-2 -methylphenyl)- N-(4,4-difluorocyclohexyl)pyrazine-2-carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- l-oxopropan-2-yl)-2-methylphenyl)- N-(2, 2, 2-trifluoroethyl)pyrazine-2 -carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- 1 -oxopropan-2-yl)-2 -methylphenyl)- N-(l-hydroxy-2-methylpropan-2-yl)pyrazine-2-carboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- l-oxopropan-2-yl)-2-methylphenyl)- N-(tetrahydro-2H-pyran-4-yl)pyrazine-2-carboxamide;

6-(5 -(3 -acetamido- 1 , 1,1 -trifluoro-2-hydroxypropan-2-yl)-2-methylphenyl)-3 -amino- N-isopropylpyrazine-2-carboxamide; 3-amino-N-isopropyl-6-(2-methyl-5-(l,l,l-trifluoro-3-(2-fluo roacetamido)-2- hydroxypropan-2-yl)phenyl)pyrazine-2-carboxamide;

3-amino-N-isopropyl-6-(2-methyl-5-(l,l,l-trifluoro-2-hydroxy -3-(2 -hydroxy-2- methylpropanamido)propan-2-yl)phenyl)pyrazine-2-carboxamide; and

3-amino-6-(5-(3-(2-cyanoacetamido)-l,l, l-trifluoro-2-hydroxypropan-2-yl)-2- methylphenyl)-N-isopropylpyrazine-2-carboxamide;

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound is selected from:

2-(3-(5 -amino-6-((R)-2-(methoxymethyl)azetidine-l-carbonyl)pyrazin- 2-yl)-4- methylphenyl)-3,3,3-trifluoro-2-hydroxypropanamide;

2-(3-(5 -amino-6-(2,2-dimethylazetidine-l-carbonyl)pyrazin-2-yl)-4-m ethylphenyl)- 3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5-amino-6-(2,3-dihydro-lH-pyrrolo[2,3-b]pyridine-l-car bonyl)pyrazin-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(7-oxabicyclo[2.2.1]heptan-2-yl)pyrazine-2-c arboxamide;

3-amino-6-(5-(l -amino-3, 3-difluoro-2 -hydroxy- l-oxopropan-2-yl)-2-methylphenyl)- N-(2-(tetrahydrofuran-3-yl)ethyl)pyrazine-2-carboxamide; and

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(3, 3, 3-trifluoro-2-hydroxypropyl)pyrazine-2 -carboxamide;

or a pharmaceutically acceptable salt thereof.

Compound subset (B)

The present application provides, inter alia, compounds of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein:

X ¹ is N or CR ¹ ; R ¹ is selected from H, D, halo, Ci-b alkyl, Ci-b alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, CN, OH and NH ₂ ;

R ² is a C1-6 haloalkyl, wherein each halogen is independently selected from F and Cl, wherein the haloalkyl is optionally substituted with C(0)NR ^a R ^b or 1, 2, 3 or 4 independently selected R ^M substituents;

each R ^M is independently selected from D, OH, NO ₂ , CN, halo, C _1-3 alkyl, C _2-3 alkenyl, C _2-3 alkynyl, C _1-3 haloalkyl, cyano-Ci- ₃ alkyl, HO-C _1-3 alkyl, C _1-3 alkoxy-Ci- ₃ alkyl, C _3-5 cycloalkyl, C _1-3 alkoxy, C _1-3 haloalkoxy, amino, C _1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C ₁ - ₃ alkylsulfmyl, C ₁ - ₃ alkylsulfonyl, carbamyl, C ₁ - ₃ alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C _1-3 alkylcarbonyl, C _1-4 alkoxycarbonyl, C _1-3 alkylcarbonylamino, C _1-3 alkoxycarbonylamino, C _1-3 alkylcarbonyloxy, aminocarbonyloxy, C _1-3

alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C _1-3 alkylsulfonylamino, aminosulfonyl, C ₁ - ₃ alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino,

C _1-3 alkylaminosulfonylamino, di(Ci- ₃ alkyl)aminosulfonylamino, aminocarbonylamino, C _1-3 alkylaminocarbonylamino, and di(Ci- ₃ alkyl)aminocarbonylamino;

R ³ is selected from H, D, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and N¾;

R ³ is selected from H, D, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and N¾;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ , R ⁵ and R ⁶ are each independently selected from H, D, halo, CN, OH, N¾, C ₁ - ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 haloalkyl, C _1-6 haloalkoxy, cyano-Ci- ₆ alkyl, HO-C _I-6 alkyl, Ci-e alkoxy-Ci- ₆ alkyl, C _3-6 cycloalkyl, C _1-6 alkylamino, di(Ci- ₆ alkyl)amino, and C(0)NR ^a R ^b ;

each R ^a and R ^b is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered

heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a and R ^b are each optionally substituted with 1, 2, 3 or 4 independently selected R ^M substituents;

R ⁷ is selected from C ₁ - ₆ alkyl, C ₁ - ₆ haloalkyl, C ₂ - ₆ alkenyl, and C ₂ - ₆ alkynyl, wherein the C _1-6 alkyl, C _2-6 alkenyl and C _2-6 alkynyl are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7A substituents; R ⁸ and R ⁹ are each independently selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-b haloalkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, C(0)R ^b8 ,

NCN)NR ^c8 R ^d8 ,

, wherein the Ci_ ₆ alkyl, C _2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ⁸ and R ⁹ are each optionally substituted with 1, 2, 3, or 4 independently selected R ^8A substituents;

or, R ⁸ and R ⁹ , together with the N atom to which they are attached, form a 5- or 6- membered heteroaryl, or a 4-10 membered heterocycloalkyl group, wherein the 5- or 6- membered heteroaryl, or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R ^8A substituents;

each R ^7A is independently selected from D, halo, Ci-b alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-14 aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-14 aryl-Ci-6 alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-12 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a71 , SR ^a71 ,

P(0)(0R ^h71 )(0R ^l71 ), and BR ^j71 R ^k71 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, G-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl 4-12 membered heterocycloalkyl, Ce-14 aryl- C1-6 alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-14 membered heteroaryl) -C 1-6 alkyl-, and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl-, of R ^7A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

each R ^a71 , R ^b71 , R ^c71 , and R ^d71 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, G,-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4- 12 membered heterocycloalkyl, Ce-14 aryl-Ci-6 alkyl-, C3-12 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl) -C 1-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, G,-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce- ₁₄ aryl-Ci-6 alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl- of R ^{a l} . R ^b71 , R ^c71 , and R ^d71 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

or, any R ^c71 and R ^d71 attached to the same N atom, together with the N atom to which they are attached, form a 5-10-membered heteroaryl or a 4-10-membered heterocycloalkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

each R ^e71 is independently selected from H, OH, CN, Ci-b alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, G-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-14 aryl-Ci- ₆ alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl-;

each R and R ^®71 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, G,-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-14 aryl-Ci- ₆ alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^h71 and R ^l71 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, G,-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, G- ₁₄ aryl-Ci-6 alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j71 and R ^k71 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j71 and R ^k71 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^7B is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, G- ₁₀ aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a72 , SR ^a72 ,

⁷² R ^d72 , NR ^c72 S(0)R ^b72 , NR ^c72 S(0)NR ^c72 R ^d72 , NR ^c72 S(0) ₂ R ^b72 ,

2, S(0)R ^b72 , S(0)NR ^c72 R ^d72 , S(0) ₂ R ^b72 , S(0) ₂ NR ^c72 R ^d72 , 0S(0) ₂ R ^b72 , SF ₅ , P(0)R ^f72 R ^g72 , 0P(0)(0R ^h72 )(0R ^l72 ), and BR ^j72 R ^k72 , wherein the Ci-b alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- C1-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^7B are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

each R ^a72 , R ^b72 , R ^c72 , and R ^d72 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a72 , R ^b72 , R ^c72 , and R ^d72 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

or, any R ^c72 and R ^d72 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^7C substituents;

each R ^e72 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, CYm aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY ₁₀ aryl-Ci- ₆ alkyl-, C _3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^{1 2} and R ^®72 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci-6haloalkoxy, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, CY ₁₀ aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY ₁₀ aryl-Ci- ₆ alkyl-, C _3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h72 and R ¹⁷² is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C ₂ - ₆ alkenyl, C _2-6 alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j72 and R ^k72 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j72 and R ^k72 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and Ci- ₆ haloalkyl; each R ^7C is independently selected from D, halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a73 , SR ^a73 , NHOR ^a73 , C(0)R ^b73 , C(0)NR ^c73 R ^d73 , C(0)NR ^c73 (0R ^b73 ), C(0)0R ^a73 , 0C(0)R ^b73 ,

0C(0)NR ^c73 R ^d73 , NR ^c73 R ^d73 , NR ^c73 NR ^c73 R ^d73 , NR ^c73 C(0)R ^b73 , NR ^c73 C(0)0R ^a73 ,

NR ^c73 C(0)NR ^c73 R ^d73 , C(=NR ^e73 )R ^b73 , C(=NOH)R ^b73 , C(=NCN)R ^b73 , C(=NR ^e73 )NR ^c73 R ^d73 , NR ^c73 C(=NR ^e73 )NR ^c73 R ^d73 , NR ^c73 C(=NR ^e73 )R ^b73 , NR ^c73 C(=NOH)NR ^c73 R ^d73 ,

NR ^c73 C(=NCN)NR ^c73 R ^d73 , NR ^c73 S(0)R ^b73 , NR ^c73 S(0)NR ^c73 R ^d73 , NR ^c73 S(0) ₂ R ^b73 ,

NR ^c73 S(0) ₂ NR ^c73 R ^d73 , S(0)R ^b73 , S(0)NR ^c73 R ^d73 , S(0) ₂ R ^b73 , S(0) ₂ NR ^c73 R ^d73 ,

0S(0)(=NR ^e73 )R ^b73 , 0S(0) ₂ R ^b73 , SF ₅ , P(0)R ^f73 R ^g73 , 0P(0)(0R ^h73 )(0R ^l73 ),

P(0)(0R ^h73 )(0R ^l73 ), and BR ^j73 R ^k73 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl) -C 1-6 alkyl- of R ^7C are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

each R ^a73 , R ^b73 , R ^c73 , and R ^d73 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a73 , R ^b73 , R ^c73 , and R ^d73 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

or, any R ^c73 and R ^d73 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

each R ^e73 is independently selected from H, OH, CN, Ci-b alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^{1 3} and R ^®73 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci-6haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h73 and R ¹⁷³ is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j73 and R ^k73 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j73 and R ^k73 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-b alkyl and C 1-6 haloalkyl; each R ^7D is independently selected from H, D, halo, CN, NO2, SR. Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl;

each R ^a8 , R ^b8 , R ^c8 , and R ^d8 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a8 , R ^b8 , R ^c8 , and R ^d8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents; or, any R ^c8 and R ^d8 atached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

each R ^e8 is independently selected from H, OH, CN, Ci-b alkyl, Ci-b alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^8A is independently selected from D, halo, Ci-b alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ³⁸¹ , SR ³⁸¹ ,

P(0)(0R ^h81 )(0R ¹⁸¹ ), and BR ^j81 R ^k81 , wherein the C _M alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₆ -io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CYm aryl- C1-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl) -C 1-6 alkyl- of R ^8A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

each R ^a81 , R ^b81 , R ^c81 , and R ^d81 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a81 , R ^b81 , R ^c81 , and R ^d81 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents; or, any R ^c81 and R ^d81 atached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

each R ^e81 is independently selected from H, OH, CN, Ci-b alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R and R ^®81 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h81 and R ^l81 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j81 and R ^k81 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j81 and R ^k81 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; and each R ^8B is independently selected from H, D, halo, CN, NO2, SF5, Ci-6 alkyl, Ci-6 alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C 3 -7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl.

In some embodiments, either: (a) R ³ and R ³ together form an oxo group; or (b) R ⁸ is C(0)R ^b8 . In some embodiments, the present application provides a compound of Formula (X):

or a pharmaceutically acceptable salt thereof, wherein:

R ¹ is selected from H, D, halo, Ci-b alkyl, Ci-b alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, CN, OH and NH ₂ ;

R ² is a Ci- ₆ haloalkyl, wherein each halogen is independently selected from F and Cl, wherein the haloalkyl is optionally substituted with C(0)NR ^a R ^b or 1, 2, 3 or 4 independently selected R ^M substituents;

each R ^M is independently selected from D, OH, NO ₂ , CN, halo, C _1-3 alkyl, C _2-3 alkenyl, C ₂ - ₃ alkynyl, C ₁ - ₃ haloalkyl, cyano-Ci- ₃ alkyl, HO-C ₁ - ₃ alkyl, C ₁ - ₃ alkoxy-Ci- ₃ alkyl, C _3-5 cycloalkyl, C _1-3 alkoxy, C _1-3 haloalkoxy, amino, C _1-3 alkylamino, di(Ci- ₃ alkyl)amino, thio, C _1-3 alkylthio, C _1-3 alkylsulfmyl, C _1-3 alkylsulfonyl, carbamyl, C _1-3 alkylcarbamyl, di(Ci- ₃ alkyl)carbamyl, carboxy, C _1-3 alkylcarbonyl, C _1-4 alkoxycarbonyl, C _1-3 alkylcarbonylamino, Ci- ₃ alkoxycarbonylamino, C ₁ - ₃ alkylcarbonyloxy, aminocarbonyloxy, C ₁ - ₃

alkylaminocarbonyloxy, di(Ci- ₃ alkyl)aminocarbonyloxy, C _1-3 alkylsulfonylamino, aminosulfonyl, C _1-3 alkylaminosulfonyl, di(Ci- ₃ alkyl)aminosulfonyl, aminosulfonylamino, C _1-3 alkylaminosulfonylamino, di(Ci- ₃ alkyl)aminosulfonylamino, aminocarbonylamino, C _1-3 alkylaminocarbonylamino, and di(Ci- ₃ alkyl)aminocarbonylamino;

each R ³ , R ³ , and R ¹⁰ is independently selected from D, halo, Ci- ₆ alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C ₃ -io cycloalkyl-Ci- ₆ alkyl-, (5-10

membered heteroaryl) -C ₁ -6 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, CN, NO ₂ ,

S(O)NR ^cl01 R ^d101 , S(0) ₂ R ^blQ1 , S(O) ₂ NR ^cl01 R ^d101 , OS(O)(=NR ^el01 )R ^b101 , 0S(0) ₂ R ^bnn , SF ₅ , P(O)R ^fl01 R ^s101 , OP(O)(OR ^hl01 )(OR ^l101 ), P(O)(OR ^hl01 )(OR ^l101 ), and BR ^jl01 R ^k101 , wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ³ ,

R ³ , and R ¹⁰ are each optionally substituted with 1, 2, 3 or 4 independently selected R ^10A substituents,

provided that none of R ³ , R ³ , and R ¹⁰ is OH;

or, alternatively, any two of R ³ , R ³ , and R ¹⁰ together form an oxo group;

R ⁴ , R ⁵ and R ⁶ are each independently selected from H, D, halo, CN, OH, NH ₂ , Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, cyano-Ci- ₆ alkyl, HO-CI-6 alkyl, Ci-6 alkoxy-Ci-6 alkyl, C3-6 cycloalkyl, Ci-6 alkylamino, di(Ci-6 alkyl)amino, and C(0)NR ^a R ^b ;

each R ^a and R ^b is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- 6 alkyl-, and (4-7 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci-b alkyl, C ₂ -6 alkenyl, C _2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered

heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a and R ^b are each optionally substituted with 1, 2, 3 or 4 independently selected R ^M substituents;

each R ^al01 , R ^bl01 , R ^cl01 , and R ^dl01 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^UM , ^ ^{11 Ul 1} _ R ^{c Kll} _ _an( j R ^dl01 _are each optionally substituted with 1, 2, 3 or 4 independently selected R ^10A substituents;

or, any R ^cl01 and R ^dl01 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^10A substituents; each R ^el01 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^fl01 and R ^®101 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^hl01 and R ^l101 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^jl01 and R ^kl01 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^jl01 and R ^kl01 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl;

each R ^10A is independently selected from D, halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a102 , SR ^a102 , NHOR ^a102 , C(0)R ^bl ° ² , C(O)NR ^cl02 R ^d102 , C(O)NR ^cl02 (OR ^b102 ), C(0)OR ^al ° ² ,

OC(0)R ^bl ° ² , OC(O)NR ^cl02 R ^d102 , NR ^cl02 R ^d102 , NR ^cl02 NR ^cl02 R ^d102 , NR ^cl02 C(O)R ^b102 ,

NR ^cl02 C(O)OR ^a102 , NR ^cl02 C(O)NR ^cl02 R ^d102 , C(=NR ^el02 )R ^b102 , C(=NOH)R ^b102 , C(=NCN)R ^b102 , C(=NR ^el02 )NR ^cl02 R ^d102 , NR ^cl02 C(=NR ^el02 )NR ^cl02 R ^d102 , NR ^cl02 C(=NR ^el02 )R ^b102 ,

NR ^cl02 C(=NOH)NR ^cl02 R ^dl02 , NR ^cl02 C(=NCN)NR ^cl02 R ^d102 , NR ^cl02 S(O)R ^b102 ,

NR ^cl02 S(O)NR ^cl02 R ^d102 , NR ^cl02 S(O) ₂ R ^b102 , NR ^cl02 S(O) ₂ NR ^cl02 R ^d102 , S(0)R ^bl ° ² ,

S(O)NR ^cl02 R ^d102 , S(0) ₂ R ^bl ° ² , S(O) ₂ NR ^cl02 R ^d102 , OS(O)(=NR ^el02 )R ^b102 , 0S(0) ₂ R ^bl ° ² , SF ₅ , P(O)R ^fl02 R ^s102 , OP(O)(OR ^hl02 )(OR ¹¹⁰² ), P(O)(OR ^hl02 )(OR ^l102 ), and BR ^jl02 R ^k102 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^10A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^10B substituents; each R ^al02 , R ^bl02 , R ^cl02 , and R ^dl02 is independently selected from H, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^al02 , R ^bl02 , R ^cl02 , and R ^dl02 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^10B substituents;

or, any R ^cl02 and R ^dl02 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^10B substituents;

each R ^el02 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^fl02 and R ^®102 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci-6haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^hl02 and R ^l102 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^jl02 and R ^kl02 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^jl02 and R ^kl02 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^10B is independently selected from H, D, halo, CN, NO2, SR. Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C 3 -7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-Ci- ₆ alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -Ci -6 alkyl- and (4-7 membered heterocycloalkyl)-Ci-6 alkyl; and

each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-14 aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, G-14 aryl-Ci-6 alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-12 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a71 , SR ^a71 , NHOR ^a71 , C(0)R ^b71 , C(0)NR ^c71 R ^d71 , C(0)NR ^c71 (0R ^b71 ), C(0)OR ^a71 , OC(0)R ^b71 ,

0C(0)NR ^c71 R ^d71 , NR ^c71 R ^d71 , NR ^c71 NR ^c71 R ^d71 , NR ^c71 C(0)R ^b71 , NR ^c71 C(0)0R ^a71 ,

NR ^c71 C(0)NR ^c71 R ^d71 , C(=NR ^e71 )R ^b71 , C(=NOH)R ^b71 , C(=NCN)R ^b71 , C(=NR ^e71 )NR ^c71 R ^d71 , NR ^c71 C(=NR ^e71 )NR ^c71 R ^d71 , NR ^c71 C(=NR ^e71 )R ^b71 , NR ^c71 C(=NOH)NR ^c71 R ^d71 ,

NR ^c71 C(=NCN)NR ^c71 R ^d71 , NR ^c71 S(0)R ^b71 , NR ^c71 S(0)NR ^c71 R ^d71 , NR ^c71 S(0) ₂ R ^b71 ,

NR ^c71 S(0) ₂ NR ^c71 R ^d71 , S(0)R ^b71 , S(0)NR ^c71 R ^d71 , S(0) ₂ R ^b71 , S(0) ₂ NR ^c71 R ^d71 ,

0S(0)(=NR ^e71 )R ^b71 , 0S(0) ₂ R ^b71 , SF ₅ , P(0)R ^m R ^s71 , 0P(0)(0R ^h71 )(0R ^l71 ),

P(0)(0R ^h71 )(0R ^l71 ), and BR ^j71 R ^k71 , wherein the Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, G-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl 4-12 membered heterocycloalkyl, -14 aryl- C1-6 alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl) -C 1-6 alkyl-, and (4-12 membered heterocycloalkyl) -C 1-6 alkyl-, of R ^7A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

each R ^a71 , R ^b71 , R ^c71 , and R ^d71 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, G,-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4- 12 membered heterocycloalkyl, G-14 aryl-Ci-6 alkyl-, C3-12 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, G,-u aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, G-14 aryl-Ci- ₆ alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a71 , R ^b71 , R ^c71 , and R ^d71 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

or, any R ^c71 and R ^d71 attached to the same N atom, together with the N atom to which they are attached, form a 5-10-membered heteroaryl or a 4-10-membered heterocycloalkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

each R ^e71 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, G-14 aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, G-14 aryl-Ci- ₆ alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-14 membered heteroaryl)-Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^m and R ^®71 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYu aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-14 aryl-Ci-6 alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-14 membered heteroaryl)-Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^h71 and R ^l71 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- ₁₄ aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-14 aryl-Ci- ₆ alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j71 and R ^k71 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j71 and R ^k71 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^7B is independently selected from D, halo, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a72 , SR ^a72 , NHOR ^a72 , C(0)R ^b72 , C(0)NR ^c72 R ^d72 , C(0)NR ^c72 (0R ^b72 ), C(0)0R ^a72 , 0C(0)R ^b72 ,

0C(0)NR ^c72 R ^d72 , NR ^c72 R ^d72 , NR ^c72 NR ^c72 R ^d72 , NR ^c72 C(0)R ^b72 , NR ^c72 C(0)0R ^a72 ,

NR ^c72 C(0)NR ^c72 R ^d72 , C(=NR ^e72 )R ^b72 , C(=NOH)R ^b72 , C(=NCN)R ^b72 , C(=NR ^e72 )NR ^c72 R ^d72 , NR ^c72 C(=NR ^e72 )NR ^c72 R ^d72 , NR ^c72 C(=NR ^e72 )R ^b72 , NR ^c72 C(=NOH)NR ^c72 R ^d72 ,

NR ^c72 C(=NCN)NR ^c72 R ^d72 , NR ^c72 S(0)R ^b72 , NR ^c72 S(0)NR ^c72 R ^d72 , NR ^c72 S(0) ₂ R ^b72 ,

NR ^c72 S(0) ₂ NR ^c72 R ^d72 , S(0)R ^b72 , S(0)NR ^c72 R ^d72 , S(0) ₂ R ^b72 , S(0) ₂ NR ^c72 R ^d72 ,

0S(0)(=NR ^e72 )R ^b72 , 0S(0) ₂ R ^b72 , SF ₅ , P(0)R ^f72 R ^g72 , 0P(0)(0R ^h72 )(0R ^l72 ),

P(0)(0R ^h72 )(0R ^l72 ), and BR ^j72 R ^k72 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- C1-6 alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^7B are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

each R ^a72 , R ^b72 , R ^c72 , and R ^d72 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -Ci -6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ³⁷² , R ^¾72 _^ ^C _ancj R ^d72 _{are eacj1} optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

or, any R ^c72 and R ^d72 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

each R ^e72 is independently selected from H, OH, CN, Ci-b alkyl, C1-6 alkoxy, Ci- ₆ haloalkyl, Ci-6haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^{1 2} and R ^®72 is independently selected from H, Ci- ₆ alkyl, Ci-b alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h72 and R ¹⁷² is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j72 and R ^k72 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j72 and R ^k72 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^7C is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, CN, NO2, OR ^a73 , SR ^a73 , NHOR ^a73 , C(0)R ^b73 , C(0)NR ^c73 R ^d73 , C(0)NR ^c73 (0R ^b73 ), C(0)0R ^a73 , 0C(0)R ^b73 ,

P(0)(0R ^h73 )(0R ^l73 ), and BR ^j73 R ^k73 , wherein the Ci-b alkyl, C _2-6 alkenyl, C _2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CYm aryl- Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^7C are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

each R ^a73 , R ^b73 , R ^c73 , and R ^d73 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, CY10 aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY10 aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a73 , R ^b73 , R ^c73 , and R ^d73 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

or, any R ^c73 and R ^d73 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^7D substituents;

each R ^e73 is independently selected from H, OH, CN, Ci- ₆ alkyl, C1-6 alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY10 aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^{1 3} and R ^®73 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY10 aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-; each R ^h73 and R ^l73 is independently selected from H, Ci- ₆ alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j73 and R ^k73 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any R ^j73 and R ^k73 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-b alkyl and Ci-6 haloalkyl; and each R ^7D is independently selected from H, D, halo, CN, NO2, SR. Ci-b alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl.

In some embodiments, X ¹ is N.

In some embodiments, X ¹ is CR ¹ .

In some embodiments, R ¹ is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ¹ is selected from H, D, and methyl.

In some embodiments, R ¹ is H.

In some embodiments, R ² is a Ci- ₆ haloalkyl, wherein each halogen of the Ci- ₆ haloalkyl is independently selected from F and Cl.

In some embodiments, R ² is a C ₁ - ₃ haloalkyl, wherein each halogen of the C ₁ - ₃ haloalkyl is independently selected from F and Cl.

In some embodiments, R ² is selected from CF ₃ , CCI ₃ , CF ₂ H, CCfrH, CF ₂ R ^M , CCl ₂ R ^M , CFH ₂ , CCIH ₂ , CFHR ^m , CC1HR ^m , CF(R ^m ) ₂ and CC1(R ^M ) ₂ .

In some embodiments, R ² is selected from CF ₃ , CF ₂ H, CF ₂ R ^M , CFH ₂ , CFHR ^M , and CF(R ^m ) ₂ .

In some embodiments, R ^M is selected from D, halo, C _1-3 alkyl, and C _1-3 haloalkyl.

In some embodiments, R ^M is selected from halo and C _1-3 haloalkyl.

In some embodiments, R ² is Ci- ₆ haloalkyl, wherein each halogen is F.

In some embodiments, R ² is Ci- ₆ haloalkyl, wherein each halogen is Cl.

In some embodiments, R ² is selected from C¾F, CHF ₂ , CF ₃ , and CF ₂ CF ₃ .

In some embodiments, R ² is CF ₃ or CHF ₂ .

In some embodiments, R ² is CF ₃ .

In some embodiments, R ² is CH ₂ F.

In some embodiments, R ² is CHF ₂ . In some embodiments, R ² is CF ₂ CF ₃ .

In some embodiments, R ³ is selected from H, D, Ci-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and NH ₂ .

In some embodiments, R ³ selected from H, D, and Ci-b alkyl.

In some embodiments, R ³ is H or D.

In some embodiments, R ³ is H.

In some embodiments, R ³ is selected from H, D, Ci-b alkyl, C _2-6 alkenyl, C _2-6 alkynyl, and NH ₂ .

In some embodiments, R ³ is selected from H, D, and Ci-b alkyl.

In some embodiments, R ³ is H or D.

In some embodiments, R ³ is H.

In some embodiments, R ³ and R ³ together form an oxo group.

In some embodiments, R ⁴ is selected from H, D, halo, C ₁ - ₆ alkyl, Ci-b alkoxy, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, Ci-6haloalkoxy, CN, OH, and NH ₂ , wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁴ is selected from H, D, halo, CN, OH, N¾, and Ci-b alkyl.

In some embodiments, R ⁴ is selected from H, D, and Ci-b alkyl, wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁴ is H.

In some embodiments, R ⁴ is D.

In some embodiments, R ⁵ is selected from H, D, halo, C ₁ - ₆ alkyl, Ci-b alkoxy, C ₂ - ₆ alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, Ci-6haloalkoxy, CN, OH, and NH ₂ , wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁵ is selected from H, D, halo, CN, OH, N¾, and Ci-b alkyl.

In some embodiments, R ⁵ is selected from H, D, and Ci-b alkyl, wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁵ is H.

In some embodiments, R ⁵ is D.

In some embodiments, R ³ and R ⁴ are each H.

In some embodiments, R ³ and R ⁵ are each H.

In some embodiments, R ⁴ and R ⁵ are each H.

In some embodiments, R ³ , R ^3” , R ⁴ , and R ⁵ are each H.

In some embodiments, R ³ and R ³ together form an oxo group; and R ⁴ and R ⁵ are each

H. In some embodiments, R ⁶ is selected from H, D, halo, Ci- ₆ alkyl, Ci-b alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, Ci- ₆ haloalkoxy, CN, OH, and N¾, wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁶ is selected from H, D, and Ci-b alkyl, wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁶ is selected from H, D, halo, CN, OH, N¾, and Ci-b alkyl.

In some embodiments, R ⁶ is Ci-b alkyl.

In some embodiments, R ⁶ is methyl.

In some embodiments, R ⁶ is CD ₃ .

In some embodiments, R ⁶ is H.

In some embodiments, R ⁶ is D.

In some embodiments, R ⁷ is selected from Ci-b alkyl, C 1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci-b alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 independently selected R ^7A substituents.

In some embodiments, R ⁷ is Ci-b alkyl, which is optionally substituted by 1, 2, or 3 independently selected R ^7A groups.

In some embodiments, R ⁷ is Ci-b alkyl.

In some embodiments, R ⁷ is propyl.

In some embodiments, R ⁷ is C2-6 alkenyl, which is optionally substituted by 1, 2, or 3 independently selected R ^7A groups.

In some embodiments, R ⁷ is C2-6 alkenyl.

In some embodiments, R ⁷ is propenyl or butenyl.

In some embodiments, R ⁷ is prop-l-enyl or but-l-enyl.

In some embodiments, R ⁷ is C2-6 alkynyl, which is optionally substituted with 1, 2 or 3 independently selected R ^7A substituents.

In some embodiments, R ⁷ is ethynyl, propynyl, butynyl, or pentynyl, wherein the ethynyl is optionally substituted by R ^7A , and the propynyl, butynyl, and pentynyl groups are each optionally substituted by 1, 2, or 3 independently selected R ^7A groups.

In some embodiments, R ⁷ is selected from ethynyl, prop-l-ynyl, but-l-ynyl, and pent- 1-ynyl, wherein the ethynyl is substituted by R ^7A , and the prop-l-ynyl, but-l-ynyl, and pent-1- ynyl are each optionally substituted by 1, 2, or 3 independently selected R ^7A groups.

In some embodiments, R ⁷ is selected from prop-l-ynyl, but-l-ynyl, and pent-l-ynyl, wherein the prop-l-ynyl, but-l-ynyl, and pent-l-ynyl are each optionally substituted by 1, 2, or 3 independently selected R ^7A groups. In some embodiments, R ⁷ is ethynyl, wherein the ethynyl is optionally substituted by 1, 2, or 3 independently selected R ^7A groups.

In some embodiments, each R ^7A is independently selected from H, D, Ci-b alkyl, Ci- ₆ haloalkyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 4-12 membered heterocycloalkyl, wherein the Ci- ₆ alkyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, and 4-12 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, 4, or 5 independently selected R ^7B substituents.

In some embodiments, each R ^7A is independently selected from H, D, Ci- ₆ alkyl, Ci- ₆ haloalkyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 4-12 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci-6 alkyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 4-12 membered

heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-i2 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 independently selected R ^7B substituents, and wherein the connection of Ce-io aryl-Ci- ₆ alkyl-, C3-12 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)- Ci- ₆ alkyl- and (4-12 membered heterocycloalkyl)-Ci- ₆ alkyl- groups to R ⁷ (e.g, to an alkynyl group of R ⁷ ) may occur through the aforementioned ring or the Ci- ₆ alkyl group.

In some embodiments, each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, and OR ^a71 , wherein the Ci-b alkyl, C 6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups.

In some embodiments, each R ^a71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, each R ^7A is independently selected from D, halo, Ci-b alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, and OR ^a71 , wherein the Ci- ₆ alkyl, C 6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups; and

each R ^a71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, each R ^7A is independently selected from Ci- ₆ alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, and OR ^a71 , wherein the Ci-b alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups. In some embodiments, each R ^7A is independently selected from methyl, cyclopropyl, pyrazolyl, imidazolyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazopyrazinyl, hydroxyl, and methoxy, wherein the cyclopropyl, pyrazolyl, imidazolyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazopyrazinyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups.

In some embodiments, each R ^7B is independently selected from halo, Ci- ₆ alkyl, CN, cyano-Ci- ₆ alkyl, and OR ^a72 .

In some embodiments, each R ^a72 is independently selected from H and Ci-b alkyl.

In some embodiments, each R ^7B is independently selected from halo, Ci- ₆ alkyl, CN, cyano-Ci- ₆ alkyl, and OR ^a72 ; and

each R ^a72 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, each R ^7A is independently selected from Ci- ₆ alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, and OR ^a71 , wherein the Ci- ₆ alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups and

each R ^7B is independently selected from halo, Ci- ₆ alkyl, CN, cyano-Ci- ₆ alkyl, and

OR ^a72 .

In some embodiments, each R ^7A is independently selected from methyl, cyclopropyl, pyrazolyl, imidazolyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazopyrazinyl, hydroxyl, and methoxy, wherein the cyclopropyl, pyrazolyl, imidazolyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazopyrazinyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups; and

each R ^7B is independently selected from methyl, cyano, cyanomethyl, and methoxy.

In some embodiments, R ⁷ is selected from Ci-6 haloalkyl.

In some embodiments, R ⁷ is trifluoromethyl.

In some embodiments, R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, C3-10 cycloalkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C3-10 cycloalkyl.

In some embodiments, R ⁸ is selected from H, Ci- ₆ alkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is H or Ci- ₆ alkyl.

In some embodiments, R ⁸ is H, methyl, ethyl, propyl or isopropyl. In some embodiments, R ⁸ is H or C(0)R ^b8 .

In some embodiments, R ⁸ is H.

In some embodiments, R ⁸ is C(0)R ^b8 .

In some embodiments, R ^b8 is selected from H, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci-b alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents.

In some embodiments, R ^b8 is selected from H, Ci-b alkyl, and Ci- ₆ haloalkyl, wherein the C1-6 alkyl of R ^b8 is optionally substituted with 1 or 2 R ^8A substituents independently selected from D, halo, CN, NO2, OH, and SH.

In some embodiments, R ^b8 is selected from methyl, fluoromethyl, cyanomethyl, and hydroxypropyl.

In some embodiments, R ^b8 is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ^b8 is selected from H, D, and methyl.

In some embodiments, R ^b8 is H.

In some embodiments, R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl and C3-10 cycloalkyl.

In some embodiments, R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci- ₆ haloalkyl.

In some embodiments, R ⁹ is H or Ci- ₆ alkyl.

In some embodiments, R ⁹ is selected from H, methyl, ethyl, propyl, and isopropyl.

In some embodiments, R ⁹ is H.

In some embodiments, R ⁸ and R ⁹ are each H.

In some embodiments:

R ³ is selected from H, D, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and

NH ₂ ;

R ³ is selected from H, D, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and NH ₂ ; and

R ⁸ is C(0)R ^b8 .

In some embodiments:

R ³ and R ³ together form an oxo group; and

R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C3-7 cycloalkyl.

In some embodiments:

X ¹ is N or CH; R ² is a Ci- ₆ haloalkyl, wherein each halogen of the Ci- ₆ haloalkyl is independently selected from F and Cl;

R ³ is selected from H, D, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and NH ₂ ;

R ³ is selected from H, D, Ci-b alkyl, C ₂ -6 alkenyl, C ₂ -6 alkynyl, Ci- ₆ haloalkyl, C3- ₁₀ cycloalkyl, 4-10 membered heterocycloalkyl, and NH ₂ ;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁵ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁶ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁷ is selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 independently selected R ^7A substituents;

R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C(0)R ^b8 ;

R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci- ₆ haloalkyl; each R ^7A is independently selected from D, halo, Ci-b alkyl, Ce-io aryl, C3- ₁₀ cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO ₂ , and OR ^a71 , wherein the Ci- ₆ alkyl, C _6-10 aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups;

each R ^a71 is independently selected from H and Ci- ₆ alkyl;

each R ^7B is independently selected from halo, Ci- ₆ alkyl, CN, cyano-Ci- ₆ alkyl, and

OR ³⁷² ;

each R ^a72 is independently selected from H and Ci- ₆ alkyl;

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents; and

each R ^8A is independently selected from D, halo, CN, NO2, OH, and SH.

In some embodiments:

X ¹ is N or CH;

R ² is a C _1-3 haloalkyl, wherein each halogen of the C _1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H; or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is selected from H and Ci-b alkyl;

R ⁵ is selected from H and Ci-b alkyl;

R ⁶ is selected from H and Ci-b alkyl;

R ⁷ is selected from Ci- ₆ alkyl, Ci-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, and OR ^a71 , wherein the Ci- ₆ alkyl, C 6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups;

each R ^a71 is independently selected from H and Ci-b alkyl;

each R ^7B is independently selected from halo, Ci- ₆ alkyl, CN, cyano-Ci- ₆ alkyl, and

OR ³⁷² ;

each R ^a72 is independently selected from H and Ci- ₆ alkyl;

R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H;

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents; and

each R ^8A is independently selected from D, halo, CN, NO2, OH, and SH.

In some embodiments:

X ¹ is N or CH;

R ² is a Ci- ₃ haloalkyl, wherein each halogen of the C1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is H;

R ⁵ is H;

R ⁶ is Ci- ₆ alkyl;

R ⁷ is selected from trifluoromethyl, propyl, propenyl, ethynyl, propynyl, butynyl, and pentynyl, wherein the ethynyl is optionally substituted by R ^7A , and the propynyl, butynyl, and pentynyl groups are each optionally substituted by 1, 2, or 3 independently selected R ^7A groups;

each R ^7A is independently selected from Ci- ₆ alkyl, G-m aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, and OR ^a71 , wherein the Ci- ₆ alkyl, G- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups;

each R ^7B is independently selected from halo, Ci- ₆ alkyl, CN, cyano-Ci- ₆ alkyl, and

OR ³⁷² ;

each R ^a72 is independently selected from H and Ci-b alkyl;

R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H; and

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

In some embodiments:

X ¹ is N or CH;

R ² is a C1-3 haloalkyl, wherein each halogen of the C1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is H;

R ⁵ is H;

R ⁶ is Ci- ₆ alkyl;

R ⁷ is selected from trifluoromethyl, propyl, propenyl, ethynyl, propynyl, butynyl, and pentynyl, wherein the ethynyl is optionally substituted by R ^7A , and the propynyl, butynyl, and pentynyl groups are each optionally substituted by 1, 2, or 3 independently selected R ^7A groups;

each R ^7A is independently selected from methyl, cyclopropyl, pyrazolyl, imidazolyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazopyrazinyl, hydroxyl, and methoxy, wherein the cyclopropyl, pyrazolyl, imidazolyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazopyrazinyl of R ^7A are each optionally substituted by 1 or 2 independently selected R ^7B groups;

each R ^7B is independently selected from methyl, cyano, cyanomethyl, and methoxy;

R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H; and

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl. In some embodiments, the compound of Formula (I) is a compound of Formula (II):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (III):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (IV):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula

(IVa):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (V):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (VI):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula (VII):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula

(Vila):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula

(VIII):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (IX):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound is selected from:

2-(3-(5 -amino-6-(prop- 1 -en- 1 -yl)pyrazin-2-yl)-4-methylphenyl)-3 ,3 ,3 -trill uoro-2- hydroxypropanamide;

2-(3-(5-amino-6-propylpyrazin-2-yl)-4-methylphenyl)-3,3,3-tr ifluoro-2- hydroxypropanamide;

2-(3-(5-amino-6-(trifluoromethyl)pyrazin-2-yl)-4-methylpheny l)-3,3,3-triiluoro-2- hydroxypropanamide;

2-(3 -(5 -amino-6-(3 -methoxyprop- 1 -ynyl)pyrazin-2-yl)-4-methylphenyl)-3 ,3 ,3 - trilluoro-2-hydroxypropanamide trifluoroacetate ;

2-(3-(5-amino-6-(cyclopropylethynyl)pyrazin-2-yl)-4-methylph enyl)-3,3,3-trifluoro- 2-hydroxypropanamide;

2-(3 -(5 -amino-6-(3 -methylbut- 1 -ynyl)pyrazin-2-yl)-4 -methylphenyl) -3,3,3 -trifluoro- 2-hydroxypropanamide;

2-(3 -(5 -amino-6-(3 -hydroxy-3 -methylbut- 1 -ynyl)pyrazin-2-yl) -4-methylphenyl)- 3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3 -(5 -amino-6-(4-hydroxypent- 1 -ynyl)pyrazin-2-yl)-4-methylphenyl)-3 ,3 ,3- trifluoro-2-hydroxypropanamide ;

2-(3-(6-((l H-pyrazol- 5 -yl)ethynyl) -5 -aminopyrazin-2-y l)-4-methylphenyl)-3 ,3,3- trilluoro-2-hydroxypropanamide ;

2-(3-(5 -amino-6-((l-methyl-lH-imidazol-5-yl)ethynyl)pyrazin-2-yl)-4 - methylphenyl)-3,3,3-triiluoro-2 -hydroxypropanamide;

2-(3-(5 -amino-6-((l -methyl-1 H-pyrazol -4-yl)ethynyl)pyrazin-2-yl)-4-methylphenyl)- 3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ; 2-(3-(5-amino-6-(pyridin-2-ylethynyl)pyrazin-2-yl)-4-methylp henyl)-3,3,3-trifluoro-

2-hydroxypropanamide;

2-(3-(5-amino-6-(pyrimidin-5-ylethynyl)pyrazin-2-yl)-4-methy lphenyl)-3,3,3- trifluoro-2-hydroxypropanamide ;

2-(3-(5-amino-6-(pyrazin-2-ylethynyl)pyrazin-2-yl)-4-methylp henyl)-3,3,3-trifluoro-

2-hydroxypropanamide;

2-(3-(5-amino-6-((4-cyanophenyl)ethynyl)pyrazin-2-yl)-4-meth ylphenyl)-3,3,3- trifluoro-2-hydroxypropanamide ;

2-(3-(5 -amino-6-((4-(cyanomethyl)phenyl)ethynyl)pyrazin-2-yl)-4-met hylphenyl)- 3,3,3-trifluoro-2-hydroxypropanamide;

2-(3-(5 -amino-6-((3,5-dimethoxyphenyl)ethynyl)pyrazin-2-yl)-4-methy lphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5 -amino-6-((3-fluorophenyl)ethynyl)pyrazin-2-yl)-4-methylphen yl)-3,3,3- trifluoro-2-hydroxypropanamide ;

2-(3-(5-amino-6-(3-hydroxy-3,4-dimethylpent-l-ynyl)pyrazin-2 -yl)-4-methylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5 -amino-6-((tetrahydro-2H-pyran-4-yl)ethynyl)pyrazin-2-yl)-4- methylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5 -amino-6-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyrazin- 2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3-(5 -amino-6-((3-hydroxy-f-methyl-2-oxopyrrolidin-3-yl)ethynyl)p yrazin-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3-(5 -amino-6-((5-methylpyrazin-2-yl)ethynyl)pyrazin-2-yl)-4-meth ylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5-amino-6-((5-methoxypyrazin-2-yl)ethynyl)pyrazin-2-yl )-4-methylphenyl)-

3, 3, 3-trifluoro-2 -hydroxypropanamide; and

2-(3-(5 -amino-6-(imidazo[l,2-a]pyrazin-6-ylethynyl)pyrazin-2-yl)-4- methylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide

or a pharmaceutically acceptable salt thereof. Compound subset (C)

The present application provides, inter alia, compounds of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein:

X ¹ is N or CR ¹ ;

R ¹ is selected from H, D, halo, Ci-b alkyl, Ci-b alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, CN, OH and N¾;

R ² is a Ci- ₆ haloalkyl, wherein each halogen is independently selected from F and Cl, wherein the haloalkyl is optionally substituted with C(0)NR ^a R ^b or 1, 2, 3 or 4 independently selected R ^M substituents;

each R ^M is independently selected from D, OH, NO ₂ , CN, halo, C _1-3 alkyl, C _2-3 alkenyl, C ₂ - ₃ alkynyl, C ₁ - ₃ haloalkyl, cyano-Ci- ₃ alkyl, HO-C ₁ - ₃ alkyl, C ₁ - ₃ alkoxy-Ci- ₃ alkyl, C _3-5 cycloalkyl, C _1-3 alkoxy, C _1-3 haloalkoxy, amino, C _1-3 alkylamino, di(Ci- ₃ alkyl)amino, thio, C _1-3 alkylthio, C _1-3 alkylsulfmyl, C _1-3 alkylsulfonyl, carbamyl, C _1-3 alkylcarbamyl, di(Ci- ₃ alkyl)carbamyl, carboxy, C ₁ - ₃ alkylcarbonyl, C _1-4 alkoxycarbonyl, C ₁ - ₃ alkylcarbonylamino, C _1-3 alkoxycarbonylamino, C _1-3 alkylcarbonyloxy, aminocarbonyloxy, C _1-3

alkylaminocarbonyloxy, di(Ci- ₃ alkyl)aminocarbonyloxy, C _1-3 alkylsulfonylamino, aminosulfonyl, C _1-3 alkylaminosulfonyl, di(Ci- ₃ alkyl)aminosulfonyl, aminosulfonylamino, Ci- ₃ alkylaminosulfonylamino, di(Ci- ₃ alkyl)aminosulfonylamino, aminocarbonylamino, C ₁ - ₃ alkylaminocarbonylamino, and di(Ci- ₃ alkyl)aminocarbonylamino;

R ³ is selected from H, D, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and N¾;

R ³ is selected from H, D, Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and NH ₂ ;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ , R ⁵ and R ⁶ are each independently selected from H, D, halo, CN, OH, N¾, Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C ₁ -6 haloalkoxy, cyano-Ci- ₆ alkyl, HO-C _I - ₆ alkyl, Ci-e alkoxy-Ci- ₆ alkyl, C3-6 cycloalkyl, Ci-b alkylamino, di(Ci-6 alkyl)amino, and C(0)NR ^a R ^b ;

each R ^a and R ^b is independently selected from H, Ci-b alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-Ci- ₆ alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered

heterocycloalkyl, phenyl-Ci- ₆ alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-6 membered heteroaryl)-Ci- ₆ alkyl-, and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a and R ^b are each optionally substituted with 1, 2, 3 or 4 independently selected R ^M substituents;

R ⁷ is selected from CYu aryl, 5-14 membered heteroaryl and C(0)NR ^c7 R ^c8 , wherein the Ce-14 aryl and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7A substituents;

each R ^c7 and R ^d7 is independently selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-14 aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl and 4-12 membered heterocycloalkyl, wherein the Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, CYu aryl, C3-12 cycloalkyl, 5-14 membered heteroaryl and 4-12 membered heterocycloalkyl of R ^c7 and R ^d7 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7A substituents;

provided that at least one of R ^c7 and R ^d7 is O,-u aryl or 5-14 membered heteroaryl;

R ⁸ and R ⁹ are each independently selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-b haloalkyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY10 aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, C(0)R ^b8 ,

NCN)NR ^c8 R ^d8 ,

, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY10 aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ⁸ and R ⁹ are each optionally substituted with 1, 2, 3, or 4 independently selected R ^8A substituents;

or, R ⁸ and R ⁹ , together with the N atom to which they are attached, form a 5- or 6- membered heteroaryl, or a 4-10 membered heterocycloalkyl group, wherein the 5- or 6- membered heteroaryl, or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R ^8A substituents;

each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, CY ₁₀ aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, N0 ₂ , OR ^a71 , SR ^a71 , NHOR ^a71 , C(0)R ^b71 , C(0)NR ^c71 R ^d71 ,

P(0)(0R ^h71 )(0R ^l71 ), and BR ^j71 R ^k71 , wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4- 10 membered heterocycloalkyl, of R ^7A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents; each R ^a71 , R ^b71 , R ^c71 , and R ^d71 is independently selected from H, Ci-b alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a71 , R ^b71 , R ^c71 , and R ^d71 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7B substituents;

or, any R ^c71 and R ^d71 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^7B substituents;

each R ^e71 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^m and R ^®71 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-; each R ^h71 and R ^l71 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j71 and R ^k71 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any R ^j71 and R ^k71 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-b alkyl and Ci-6 haloalkyl; each R ^7B is independently selected from D, halo, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a72 , SR ^a72 , NHOR ^a72 , C(0)R ^b72 , C(0)NR ^c72 R ^d72 , C(0)NR ^c72 (0R ^b72 ), C(0)0R ^a72 , 0C(0)R ^b72 ,

0C(0)NR ^c72 R ^d72 , NR ^c72 R ^d72 , NR ^c72 NR ^c72 R ^d72 , NR ^c72 C(0)R ^b72 , NR ^c72 C(0)0R ^a72 ,

NR ^c72 C(0)NR ^c72 R ^d72 , C(=NR ^e72 )R ^b72 , C(=NOH)R ^b72 , C(=NCN)R ^b72 , C(=NR ^e72 )NR ^c72 R ^d72 , NR ^c72 C(=NR ^e72 )NR ^c72 R ^d72 , NR ^c72 C(=NR ^e72 )R ^b72 , NR ^c72 C(=NOH)NR ^c72 R ^d72 ,

NR ^c72 C(=NCN)NR ^c72 R ^d72 , NR ^c72 S(0)R ^b72 , NR ^c72 S(0)NR ^c72 R ^d72 , NR ^c72 S(0) ₂ R ^b72 ,

NR ^c72 S(0) ₂ NR ^c72 R ^d72 , S(0)R ^b72 , S(0)NR ^c72 R ^d72 , S(0) ₂ R ^b72 , S(0) ₂ NR ^c72 R ^d72 ,

0S(0)(=NR ^e72 )R ^b72 , 0S(0) ₂ R ^b72 , SF ₅ , P(0)R ^f72 R ^g72 , 0P(0)(0R ^h72 )(0R ^l72 ),

P(0)(0R ^h72 )(0R ^l72 ), and BR ^j72 R ^k72 , wherein the Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- C1-6 alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^7B are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

each R ^a72 , R ^b72 , R ^c72 , and R ^d72 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a72 , R ^b72 , R ^c72 , and R ^d72 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents; or, any R ^c72 and R ^d72 atached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7C substituents;

each R ^e72 is independently selected from H, OH, CN, Ci-b alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^{1 2} and R ^®72 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^h72 and R ¹⁷² is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j72 and R ^k72 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j72 and R ^k72 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and C 1-6 haloalkyl; each R ^7C is independently selected from D, halo, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ^a73 , SR ^a73 ,

P(0)(0R ^h73 )(0R ^l73 ), and BR ^j73 R ^k73 , wherein the Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl- C1-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^7C are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

each R ^a73 , R ^b73 , R ^c73 , and R ^d73 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a73 , R ^b73 , R ^c73 , and R ^d73 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

or, any R ^c73 and R ^d73 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^7D substituents;

each R ^e73 is independently selected from H, OH, CN, Ci- ₆ alkyl, C1-6 alkoxy, Ci- ₆ haloalkyl, Ci-6haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^{1 3} and R ^®73 is independently selected from H, Ci- ₆ alkyl, Ci-b alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h73 and R ¹⁷³ is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^j73 and R ^k73 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy; or any R ^j73 and R ^k73 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-b alkyl and Ci- ₆ haloalkyl; each R ^7D is independently selected from H, D, halo, CN, NO2, SR. Ci-b alkyl, Ci- ₆ alkoxy, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci-6 alkyl;

each R ^a8 , R ^b8 , R ^c8 , and R ^d8 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl- of R ^a8 , R ^b8 , R ^c8 , and R ^d8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

or, any R ^c8 and R ^d8 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

each R ^e8 is independently selected from H, OH, CN, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci-6 alkyl-;

each R ^8A is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci-6 alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, CN, NO2, OR ³⁸¹ , SR ³⁸¹ ,

P(0)(0R ^h81 )(0R ^l81 ), and BR ^j81 R ^k81 , wherein the C _M alkyl, C _2.6 alkenyl, C _2.6 alkynyl, C ₆ -io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl- Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^8A are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

each R ^a81 , R ^b81 , R ^c81 , and R ^d81 is independently selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl) -C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-io aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl- of R ^a81 , R ^b81 , R ^c81 , and R ^d81 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8B substituents;

or, any R ^c81 and R ^d81 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1 , 2, 3 or 4 independently selected R ^8B substituents;

each R ^e81 is independently selected from H, OH, CN, Ci- ₆ alkyl, C1-6 alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY ₁₀ aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R and R ^®81 is independently selected from H, Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, CYm aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY ₁₀ aryl-Ci- ₆ alkyl-, C3-10 cycloalkyl-Ci- ₆ alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-;

each R ^h81 and R ^l81 is independently selected from H, Ci- ₆ alkyl, C 1-6 haloalkyl, C _2-6 alkenyl, C ₂ - ₆ alkynyl, CY10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CY10 aryl-Ci- ₆ alkyl-, C3-io cycloalkyl-Ci-6 alkyl-, (5-10 membered heteroaryl)-Ci- ₆ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₆ alkyl-; each R ^j81 and R ^k81 is independently selected from OH, Ci- ₆ alkoxy, and Ci- ₆ haloalkoxy;

or any R ^j81 and R ^k81 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- ₆ alkyl and Ci-6 haloalkyl; and each R ^8B is independently selected from H, D, halo, CN, NO2, SR. Ci- ₆ alkyl, Ci- ₆ alkoxy, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C3-7 cycloalkyl-Ci-6 alkyl-, (5-7 membered heteroaryl) -C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-Ci- ₆ alkyl.

In some embodiments, either: (a) R ³ and R ³ together form an oxo group; or (b) R ⁸ is C(0)R ^b8 .

In some embodiments, X ¹ is N.

In some embodiments, X ¹ is CR ¹ .

In some embodiments, R ¹ is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ¹ is selected from H, D, and methyl.

In some embodiments, R ¹ is H.

In some embodiments, R ² is a Ci- ₆ haloalkyl, wherein each halogen of the Ci- ₆ haloalkyl is independently selected from F and Cl.

In some embodiments, R ² is a C _1-3 haloalkyl, wherein each halogen of the C _1-3 haloalkyl is independently selected from F and Cl.

In some embodiments, R ² is selected from CF ₃ , CCI ₃ , CF ₂ H, CCFH, CF ₂ R ^M , CChR ^M , CFH ₂ , CCIH ₂ , CFHR ^m , CC1HR ^m , CF(R ^m ) ₂ and CC1(R ^M ) ₂ .

In some embodiments, R ² is selected from CF ₃ , CF ₂ H, CF ₂ R ^M , CF¾, CFHR ^M , and CF(R ^m ) ₂ .

In some embodiments, R ^M is selected from D, halo, C ₁ - ₃ alkyl, and C ₁ - ₃ haloalkyl.

In some embodiments, R ^M is selected from halo and C _1-3 haloalkyl.

In some embodiments, R ² is Ci- ₆ haloalkyl, wherein each halogen is F.

In some embodiments, R ² is Ci- ₆ haloalkyl, wherein each halogen is Cl.

In some embodiments, R ² is selected from C¾F, CHF ₂ , CF ₃ , and CF ₂ CF ₃ .

In some embodiments, R ² is CF ₃ or CHF ₂ .

In some embodiments, R ² is CF ₃ .

In some embodiments, R ² is CH ₂ F.

In some embodiments, R ² is CHF2.

In some embodiments, R ² is CF ₂ CF ₃ . In some embodiments, R ³ is selected from H, D, Ci-6 alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, C _1-6 haloalkyl, and NH ₂ .

In some embodiments, R ³ selected from H, D, and C _1-6 alkyl.

In some embodiments, R ³ is H or D.

In some embodiments, R ³ is H.

In some embodiments, R ³ is selected from H, D, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, and NH ₂ .

In some embodiments, R ³ is selected from H, D, and C _1-6 alkyl.

In some embodiments, R ³ is H or D.

In some embodiments, R ³ is H.

In some embodiments, R ³ and R ³ together form an oxo group.

In some embodiments, R ⁴ is selected from H, D, halo, C _1-6 alkyl, C _1-6 alkoxy, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C ₁ - ₆ haloalkyl, Ci-6haloalkoxy, CN, OH, and N¾, wherein the C ₁ - ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁴ is selected from H, D, halo, CN, OH, N¾, and C _1-6 alkyl.

In some embodiments, R ⁴ is selected from H, D, and C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁴ is H.

In some embodiments, R ⁴ is D.

In some embodiments, R ⁵ is selected from H, D, halo, C _1-6 alkyl, C _1-6 alkoxy, C _2-6 alkenyl, C ₂ - ₆ alkynyl, C ₁ - ₆ haloalkyl, Ci-6haloalkoxy, CN, OH, and N¾, wherein the C ₁ - ₆ alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁵ is selected from H, D, halo, CN, OH, N¾, and C _1-6 alkyl.

In some embodiments, R ⁵ is selected from H, D, and C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁵ is H.

In some embodiments, R ⁵ is D.

In some embodiments, R ³ and R ⁴ are each H.

In some embodiments, R ³ and R ⁵ are each H.

In some embodiments, R ⁴ and R ⁵ are each H.

In some embodiments, R ³ , R ³ , R ⁴ , and R ⁵ are each H.

In some embodiments, R ³ and R ³ together form an oxo group; and R ⁴ and R ⁵ are each

H. In some embodiments, R ⁶ is selected from H, D, halo, Ci- ₆ alkyl, Ci-b alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, Ci- ₆ haloalkoxy, CN, OH, and N¾, wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁶ is selected from H, D, and Ci-b alkyl, wherein the Ci-b alkyl is optionally substituted with 1, 2, or 3 deuterium atoms.

In some embodiments, R ⁶ is selected from H, D, halo, CN, OH, N¾, and Ci-b alkyl.

In some embodiments, R ⁶ is Ci-b alkyl.

In some embodiments, R ⁶ is methyl.

In some embodiments, R ⁶ is CD3.

In some embodiments, R ⁶ is H.

In some embodiments, R ⁶ is D.

In some embodiments, R ⁷ is selected from phenyl, 5-10 membered heteroaryl, and C(0)NR ^C7 R ^c8 , wherein the phenyl and 5-10 membered heteroaryl of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents.

In some embodiments, R ⁷ is selected from phenyl, a monocyclic 5-6 membered heteroaryl, and C(0)NR ^c7 R ^c8 , wherein the phenyl and monocyclic 5-6 membered heteroaryl of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents.

In some embodiments, R ⁷ is selected from phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, and pyrimidinyl, wherein the phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, and pyrimidinyl, of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents.

In some embodiments, each R ^7A is independently selected from D, halo, Ci-b alkyl, C1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, CYm aryl, C(0)NR ^c71 R ^d71 , and BR ⁾⁷¹ R ^k71 , wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, and Ce-io aryl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents.

In some embodiments, each R ^7A is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH) ₂ , wherein the Ci- ₆ alkyl and C _3-10 cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents.

In some embodiments, each R ^7B is independently selected from CN, OH, C 1-3 alkoxy, and C3-6 cycloalkyl.

In some embodiments, each R ^7A is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C3- ₁₀ cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH)2, wherein the Ci- ₆ alkyl and C3- ₁₀ cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents selected from CN, OH, C _1-3 alkoxy, and C _3-6 cycloalkyl. In some embodiments, each R ^c71 and R ^d71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, each R ^7A is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH) ₂ , wherein the Ci- ₆ alkyl and C _3-10 cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents selected from CN, OH, C _1-3 alkoxy, and C _3-6 cycloalkyl; and

each R ^c71 and R ^d71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, R ⁷ is selected from phenyl, 5-10 membered heteroaryl, and C(0)NR ^C7 R ^c8 , wherein the phenyl and 5-10 membered heteroaryl of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents; and

each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, Ce-io aryl, C(0)NR ^c71 R ^d71 , and BR ^j71 R ^k71 , wherein the Ci- ₆ alkyl, C ₂ -6 alkenyl, C ₂ -6 alkynyl, C3- ₁₀ cycloalkyl, and Ce-io aryl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents.

In some embodiments, R ⁷ is selected from phenyl, 5-10 membered heteroaryl, and C(0)NR ^C7 R ^c8 , wherein the phenyl and 5-10 membered heteroaryl of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents; and

each R ^7A is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH) ₂ , wherein the Ci- ₆ alkyl and C _3-10 cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents selected from CN, OH, Ci- ₃ alkoxy, and C3-6 cycloalkyl.

In some embodiments, R ⁷ is selected from phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, and pyrimidinyl, wherein the phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, and pyrimidinyl, of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

each R ^7A is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH) ₂ , wherein the Ci- ₆ alkyl and C _3-10 cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents selected from CN, OH, Ci- ₃ alkoxy, and C3-6 cycloalkyl; and

each R ^c71 and R ^d71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is selected from H, Ci- ₆ alkyl, C ₂ -6 alkenyl, C ₂ -6 alkynyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, and C(0)R ^b8 . In some embodiments, R ⁸ is selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- 6 haloalkyl, and C3-10 cycloalkyl.

In some embodiments, R ⁸ is selected from H, Ci-b alkyl, and C(0)R ^b8 .

In some embodiments, R ⁸ is H or Ci-b alkyl.

In some embodiments, R ⁸ is H, methyl, ethyl, propyl or isopropyl.

In some embodiments, R ⁸ is H or C(0)R ^b8 .

In some embodiments, R ⁸ is H.

In some embodiments, R ⁸ is C(0)R ^b8 .

In some embodiments, R ^b8 is selected from H, Ci-b alkyl, Ci-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci-b alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents.

In some embodiments, R ^b8 is selected from H, Ci-b alkyl, and Ci-b haloalkyl, wherein the Ci- ₆ alkyl of R ^b8 is optionally substituted with 1 or 2 R ^8A substituents independently selected from D, halo, CN, NO2, OH, and SH.

In some embodiments, R ^b8 is selected from methyl, fluoromethyl, cyanomethyl, and hydroxypropyl.

In some embodiments, R ^b8 is selected from H, D, and Ci- ₆ alkyl.

In some embodiments, R ^b8 is selected from H, D, and methyl.

In some embodiments, R ^b8 is H.

In some embodiments, R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- 6 haloalkyl and C3-10 cycloalkyl.

In some embodiments, R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci- ₆ haloalkyl.

In some embodiments, R ⁹ is H or Ci- ₆ alkyl.

In some embodiments, R ⁹ is selected from H, methyl, ethyl, propyl, and isopropyl.

In some embodiments, R ⁹ is H.

In some embodiments, R ⁸ and R ⁹ are each H.

In some embodiments:

R ³ is selected from H, D, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-b haloalkyl, and

NH ₂ ;

R ³ is selected from H, D, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and NH ₂ ; and

R ⁸ is C(0)R ^b8 .

In some embodiments:

R ³ and R ³ together form an oxo group; and R ⁸ is selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-b haloalkyl, and C3-7 cycloalkyl.

In some embodiments:

X ¹ is N or CH;

R ² is a Ci- ₆ haloalkyl, wherein each halogen of the Ci- ₆ haloalkyl is independently selected from F and Cl;

R ³ is selected from H, D, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and

NH ₂ ;

R ³ is selected from H, D, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and

NH ₂ ;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁵ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁶ is selected from H, D, halo, CN, OH, N¾, and Ci- ₆ alkyl;

R ⁷ is selected from phenyl, 5-10 membered heteroaryl, and C(0)NR ^c7 R ^c8 , wherein the phenyl and 5-10 membered heteroaryl of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

each R ^7A is independently selected from D, halo, Ci- ₆ alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, CY m aryl, C(0)NR ^c71 R ^d71 , and BR ^j71 R ^k71 , wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and CY m aryl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents;

each R ^7B is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, halo CN, OH, Ci- ₆ alkoxy, and C3-6 cycloalkyl;

R ⁸ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci- ₆ haloalkyl, and C(0)R ^b8 ;

R ⁹ is selected from H, Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci- ₆ haloalkyl;

R ^b8 is selected from H, Ci- ₆ alkyl, Ci- ₆ haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

each R ^8A is independently selected from D, halo, CN, NO2, OH, and SH;

each R ^c71 and R ^d71 is independently selected from H and Ci- ₆ alkyl; and

each R ^j71 and R ^k71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments:

X ¹ is N or CH; R ² is a Ci- ₃ haloalkyl, wherein each halogen of the C 1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is selected from H and C1-6 alkyl;

R ⁵ is selected from H and C1-6 alkyl;

R ⁶ is selected from H and C1-6 alkyl;

R ⁷ is selected from phenyl, 5-10 membered heteroaryl, and C(0)NR ^c7 R ^c8 , wherein the phenyl and 5-10 membered heteroaryl of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

each R ^7A is independently selected from C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH)2, wherein the Ci- ₆ alkyl and C3- ₁₀ cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents;

each R ^7B is independently selected from CN, OH, C1-3 alkoxy, and C3-6 cycloalkyl;

R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H;

R ^b8 is selected from H, Ci- ₆ alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, and C2-6 alkynyl of R ^b8 are each optionally substituted with 1, 2, 3 or 4 independently selected R ^8A substituents;

each R ^8A is independently selected from D, halo, CN, NO2, OH, and SH; and each R ^c71 and R ^d71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments:

X ¹ is N or CH;

R ² is a Ci- ₃ haloalkyl, wherein each halogen of the C 1-3 haloalkyl is independently selected from F and Cl;

R ³ is H;

R ^3” is H;

or, alternatively, R ³ and R ³ together form an oxo group;

R ⁴ is H;

R ⁵ is H;

R ⁶ is Ci- ₆ alkyl;

R ⁷ is selected from phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, and pyrimidinyl, wherein the phenyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, and pyrimidinyl, of R ⁷ are each optionally substituted with 1 or 2 independently selected R ^7A substituents;

each R ^7A is independently selected from Ci- ₆ alkyl, Ci- ₆ haloalkyl, C _3-10 cycloalkyl, C(0)NR ^c71 R ^d71 , and B(OH) ₂ , wherein the Ci- ₆ alkyl and C _3-10 cycloalkyl of R ^7A are each optionally substituted with 1 or 2 independently selected R ^7B substituents;

each R ^7B is independently selected from CN, OH, C _1-3 alkoxy, and C _3-6 cycloalkyl; R ⁸ is selected from H and C(0)R ^b8 ;

R ⁹ is H;

R ^b8 is selected from H, Ci- ₆ alkyl, Ci-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; and each R ^c71 and R ^d71 is independently selected from H and Ci- ₆ alkyl.

In some embodiments, the compound of Formula (I) is a compound of Formula (II):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (III):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula (IV):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula

(IVa):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (V):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula (VI):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (VII):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula

(Vila):

or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula

(VIII):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) is a compound of Formula (IX):

or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound is 2-(3-(5-amino-6-(l-methyl-lH-pyrazol-5- yl)pyrazin-2-yl)-4-methylphenyl)-3,3,3-trifluoro-2-hydroxypr opanamide;

2-(3-(5-amino-6-(2-methyloxazol-5-yl)pyrazin-2-yl)-4-methylp henyl)-3,3,3-trifluoro-

2-hydroxypropanamide;

2-(3-(5 -amino-6-(l -methyl-1 H-pyrazol-4-yl)pyrazin-2-yl)-4-methylphenyl)-3,3 ,3 - trifluoro-2-hydroxypropanamide ;

2-(3 -(5 -amino-6-(2-methylthiazol-5 -yl)pyrazin-2-yl)-4-methylphenyl) -3,3 ,3 -trifluoro- 2-hydroxypropanamide;

2-(3 -(5 -amino-6-(2 -methyl-211- 1 , 2,3-triazol-4-yl)pyrazin-2-yl) -4-methylphenyl)- 3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ; 2-(3 -(5 -amino-6-( 1 -methyl- 1 H- 1 , 2, 3 -triazol-5 -yl)pyrazin-2-yl) -4-methylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3 -(5 -amino-6-( 1 -(2, 2,2 -trifluoroethyl)- 1 H-pyrazol-4 -yl)pyrazin-2-yl) -4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3-(5-amino-6-(l-(2-cyanopropan-2-yl)-lH-pyrazol-4-yl)pyra zin-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3-(5 -amino-6-(l-(tetrahydro-2H-pyran-4-yl)-lH-pyrazol-4-yl)pyraz in-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3-(5-amino-6-(l-((l-cyanocyclopropyl)methyl)-lH-pyrazol-4 -yl)pyrazin-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3 -(5 -amino-6-(l -(2-methoxyethyl)- 1 H-pyrazol-4-yl)pyrazin-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

5 -(3 -amino-6 -(5 -(3 -amino- 1, 1, 1 -trifluoro-2 -hydroxy-3 -oxopropan-2-yl) -2- methylphenyl)pyrazin-2-yl)-N-methylpicolinamide;

2-(3 -(5 -amino-6-(pyrimi din-5 -yl)pyrazin-2-yl)-4 -methy lphenyl)-3 ,3 ,3 -trifluoro-2- hydroxypropanamide;

2-(3-(5 -amino-6-(6-methylpyri din-3 -yl)pyrazin-2-yl)-4-methylphenyl)-3,3 ,3 - trifluoro-2-hydroxypropanamide ;

2-(3-(5 -amino-6-(6-(trifluoromethyl)pyridin-3-yl)pyrazin-2-yl)-4-me thylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3 -(5 -amino-6-(2-cyclopropylthiazol-5 -yl)pyrazin-2-yl)-4-methylphenyl)-3 ,3 ,3- trifluoro-2-hydroxypropanamide ;

2-(3-(5 -amino-6-(2-(hydroxymethyl)pyridin-4-yl)pyrazin-2-yl)-4-meth ylphenyl)-

3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5-amino-6-(l-(cyclopropylmethyl)-lH-pyrazol-4-yl)pyraz in-2-yl)-4- methylphenyl)-3, 3, 3-trifluoro-2 -hydroxypropanamide;

2-(3 -(5 -amino-6-(4-(cyanomethyl)phenyl)pyrazin-2-yl) -4-methylphenyl)-3,3 ,3 - trifluoro-2-hydroxypropanamide ;

2-(3-(5-amino-6-(4-(hydroxymethyl)phenyl)pyrazin-2-yl)-4-met hylphenyl)-3,3,3- trifluoro-2-hydroxypropanamide ;

4-(3 -amino-6 -(5 -(3 -amino- 1, 1, 1 -trifluoro-2 -hydroxy-3 -oxopropan-2-yl) -2- methylphenyl)pyrazin-2-yl)-N-methylbenzamide;

2-(3-(5-amino-6-(3-isopropylphenyl)pyrazin-2-yl)-4-methylphe nyl)-3,3,3-trifluoro-2- hydroxypropanamide; 2-(3 -(5 -amino-6-(4-(2-hydroxypropan-2-yl)phenyl)pyrazin-2-yl)-4-met hylphenyl) - 3 ,3 ,3 -trifluoro-2 -hydroxypropanamide ;

2-(3-(5 -amino-6-(4-cyclopropylphenyl)pyrazin-2-yl)-4-methylphenyl)- 3,3,3-trifluoro- 2-hydroxypropanamide;

2-(3-(5 -amino-6-(lH-pyrazol-l-yl)pyrazin-2-yl)-4-methylphenyl)-3,3, 3-trifluoro-2- hydroxypropanamide;

2-(3-(5 -amino-6-(lH-l,2,4-triazol-l-yl)pyrazin-2-yl)-4-methylphenyl )-3,3,3- trifluoro-2-hydroxy-N-methylpropanamide;

2-(3-(5 -amino-6-(lH-l,2,4-triazol-l-yl)pyrazin-2-yl)-4-methylphenyl )-3,3,3- trifluoro-2-hydroxy-N,N-dimethylpropanamide;

2-(3-(5 -amino-6-(l-methyl-lH-pyrazol-4-yl)pyrazin-2-yl)-4-methylphe nyl)-3,3,3- trifluoro-2-hydroxy-N-methylpropanamide;

(4-(3-amino-6-(5 -(3 -amino- 1, 1, 1 -trifluoro-2 -hydroxy-3 -oxopropan-2-yl)-2- methylphenyl)pyrazin-2-yl)phenyl)boronic acid;

2-(3-(5 -amino-6-(l-methyl-lH-pyrazol-5-yl)pyrazin-2-yl)-4-methylphe nyl)-3,3- difluoro-2-hydroxypropanamide;

2-(3-(5 -amino-6-(l-methyl-lH-pyrazol-5-yl)pyrazin-2-yl)-4-methylphe nyl)-3,3- difluoro-2-hydroxypropanamide;

2-(3-(5-amino-6-(2-methyloxazol-5-yl)pyrazin-2-yl)-4-methylp henyl)-3,3-difluoro-2- hydroxypropanamide;

2-(3-(5 -amino-6-(2-methyl-2H-l,2,3-triazol-4-yl)pyrazin-2-yl)-4-met hylphenyl)-3,3- difluoro-2-hydroxypropanamide;

N-(2-(3-(5 -amino-6-(2-cyclopropylthiazol-5-yl)pyrazin-2-yl)-4-methylph enyl)-3 ,3 ,3 - trifluoro-2-hydroxypropyl)formamide;

N-(2-(3-(5 -amino-6-(lH-pyrazol-4-yl)pyrazin-2-yl)-4-methylphenyl)-3,3, 3-trifluoro- 2-hydroxypropyl)formamide;

N-(2-(3-(5 -amino-6-(l-(2,2,2-trifluoroethyl)-lH-pyrazol-4-yl)pyrazin-2 -yl)-4- methylphenyl) -3 ,3 ,3 -trifluoro-2 -hydroxypropyl) acetamide;

N-(2-(3-(5 -amino-6-(lH-pyrazol-4-yl)pyrazin-2-yl)-4-methylphenyl)-3,3, 3-trifluoro- 2-hydroxypropyl)acetamide; and

3 -amino-6-(5 -(3 -amino- 1,1,1 -trifluoro-2-hydroxy-3 -oxopropan-2 -yl) -2- methylphenyl)-N-(l-methyl-lH-pyrazol-5-yl)pyrazine-2-carboxa mide;

or a pharmaceutically acceptable salt thereof. Compound subset (D)

The present application provides, inter alia, compounds of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein:

X ¹ is N or CR ¹ ;

R ¹ is selected from H, D, halo, Ci-b alkyl, Ci-b alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, Ci- ₆ haloalkoxy, CN, OH and N¾;

R ² is a Ci- ₆ haloalkyl, wherein each halogen is independently selected from F and Cl, wherein the haloalkyl is optionally substituted with C(0)NR ^a R ^b or 1, 2, 3 or 4 independently selected R ^M substituents;

each R ^M is independently selected from D, OH, NO ₂ , CN, halo, C _1-3 alkyl, C _2-3 alkenyl, C ₂ - ₃ alkynyl, C ₁ - ₃ haloalkyl, cyano-Ci- ₃ alkyl, HO-C ₁ - ₃ alkyl, C ₁ - ₃ alkoxy-Ci- ₃ alkyl, C _3-5 cycloalkyl, C _1-3 alkoxy, C _1-3 haloalkoxy, amino, C _1-3 alkylamino, di(Ci- ₃ alkyl)amino, thio, C _1-3 alkylthio, C _1-3 alkylsulfmyl, C _1-3 alkylsulfonyl, carbamyl, C _1-3 alkylcarbamyl, di(Ci- ₃ alkyl)carbamyl, carboxy, C ₁ - ₃ alkylcarbonyl, C _1-4 alkoxycarbonyl, C ₁ - ₃ alkylcarbonylamino, C _1-3 alkoxycarbonylamino, C _1-3 alkylcarbonyloxy, aminocarbonyloxy, C _1-3