Sulfonamide derivatives as cyclin-dependent kinase 2 inhibitors

Abstract

The present disclosure provides certain sulfonamide derivatives that are Cyclin-dependent kinase 2 (CDK2) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of CDK2. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Description

SULFONAMIDE DERIVATIVES AS CYCLIN-DEPENDEN T KINASE 2 INHIBITORSThis application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 585,897, filed on September 27, 2023, the entirety of which is incorporated by reference herein.Field of the disclosureThe present disclosure provides certain sulfonamide derivatives that are cyclin-dependent kinase 2 (CDK2) inhibitors and are useful for the treatment of diseases mediated by the inhibition of CDK2. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.BackgroundCyclin-dependent kinases (CDKs) are cellular kinases that are critical for orchestrating signaling events such as DNA replication and protein synthesis to ensure faithful eukaryotic cell division and proliferation. To achieve activation, the cyclin-dependent kinase catalytic units of CDK often require binding with regulatory subunits known as cyclins. In addition, the activity of CDK is also controlled by its phosphorylation status, as well as by binding of inhibitory proteins.Of the CDKs identified thus far, at least CDKl / Cyclin B, CDK2 / Cyclin E, CDK2 / Cyclin A, CDK4 / Cyclin D, CDK6 / Cyclin D complexes are known to be important regulators of cell cycle progression; while other CDKs are important in regulating gene transcription, DNA repair, differentiation, and apoptosis (see Morgan, D. O. Annu. Rev. Cell. Dev. Biol. (1997) 13: 261-291).Due to their key roles in regulating cell cycle and other essential cellular processes, increased activity or temporally abnormal activation of CDKs has been shown to result in the development of various types of cancer. CDK2 / Cyclin E complex plays an important role in regulation of the Gl / S transition, histone biosynthesis and centrosome duplication. Following the initial phosphorylation of retinoblastoma (Rb) by CDK 4 / 6 / cyclin D, CDK2 / Cyclin E further hyper-phosphorylates p-RB, releases G1 transcription factor, E2F, to transcribe genes required for S-phase entry. During S-phase, Cyclin E is degraded and CDK2 forms a complex with Cyclin A to promote phosphorylation of substrates that permit DNA replication and inactivation of E2F, for S-phase completion (see Asghar et al. Nat. Rev. Drug. Discov. (2015) 14: 130-146). In addition to cyclin bindings, the activity of CDK2 is also tightly regulated through its interaction with negative regulators, such as p21 and p27. In response to mitogenic stimulation, which signals optimalenvironment for cell cycle, p21 and p27 are phosphorylated and degraded, releasing the break on CDK2 / Cyclin activation.Cyclin E, the regulatory cyclin for CDK2, is frequently overexpressed in cancer, and its overexpression correlates with poor prognosis. For example, Cyclin E amplification or overexpression has been shown to be associated with poor outcomes in breast cancer (see Keyomarsi et al., N Engl J Med. (2002) 347: 1566-75). Cyclin E2 (CCNE2) overexpression is associated with endocrine resistance in breast cancer cells and CDK2 inhibition has been reported to restore sensitivity to tamoxifen or CDK4 / 6 inhibitors in tamoxifen resistant and CCNE2 overexpressing cells. (See Caldon et al., Afo / Cancer Ther. (2012) 11 : 1488-99; and Herr era- Abreu et al., Cancer Res. (2016)76:2301-2313). Cyclin E amplification also reportedly contributes to trastuzumab resistance in HER2+ breast cancer. (See Scaltriti et al. Proc Natl Acad Sci. (2011) 108:3761-6). Cyclin E overexpression has also been reported to play a role in basal-like and triple negative breast cancer (TNBC), as well as inflammatory breast cancer. (See Elsawaf Z. et al. Breast Care (2011) 6:273-278; and Alexander A. et al. Oncotarget (2017) 8: 14897-14911.)Amplification or overexpression of cyclin El (CCNE1) is also frequently found in ovarian, gastric, endometrial, uterus, bladder, esophagus, prostate, lung and other types of cancers (see Nakayama et al. Cancer (2010) 116:2621-34; Etemadmoghadam et al. Clin Cancer Res (2013) 19: 5960-71; Au-Yeung et al. Clin. Cancer Res. (2017) 23: 1862-1874; Ayhan et al. Modern Pathology (2017) 30: 297-303; Ooi et al. Hum Pathol. (2017) 61 :58-67; and Noske et al. Oncotarget (2017) 8: 14794-14805) and often correlates with poor clinical outcomes.The turnover of cyclin El is regulated by the SCFFbxw7ubiquitin E3 ligase component FBXW7 and the deubiquitinase USP28, which are frequently dysregulated in cancer. Loss-of-function mutations in FBXW7 or overexpression of USP28 lead to cyclin E overexpression and CDK2 activation. (See Weicker, M. & Clurman, B. E. 2008 Nat. Rev. Cancer 8, 83; Diefenbacher, M. E. et al. (2014) J. Clin. Invest. 124, 3407-3418.) Alternatively, certain cancer cells express a hyperactive, truncated form of cyclin E. (See Caruso JA et al. Cancer Res. 2018 Oct 1 ;78(19): 5481 -5491.) In addition, cyclin A amplification and overexpression have also been reported in various cancers such as hepatocellular carcinomas (see Bayard, Q., et al. Nat Commun 9, 5235 (2018)), colorectal and breast cancers.In contrast to the frequent upregulation of Cyclin E, the inhibitory regulators of CDK2, p21 and p27 are often abnormally downregulated in cancers. SKP2, a component of the SKP1- CULl-F-box (SCF) complex, has also been implicated in tumorigenesis owing to its capacity to degrade p27. (See Zhen Cai et al., Seminars in Cancer Biology 2020 67(2): 16-33). It is postulatedthat the loss or decrease of p21 / p27 or overexpression of SKP2 lead to high and / or abnormal temporal activation of CDK2, thereby promoting oncogenic growth.In addition, CDC25 A and CDC25B, protein phosphatases responsible for the dephosphorylations that activate the CDK2, are overexpressed in various tumors. These various mechanisms of CDK2 activation have been validated using mouse cancer models.The retinoblastoma (Rb) protein functions as transcription co-repressor and represents the key substrate of CDK4 / 6 and CDK2 complexes in driving cell division. Consistent with this canonical model, Rb-defi cient tumors do not depend on CDK4 / 6 and are uniformly resistant to CDK4 / 6 inhibitors. However, an analysis on DepMAP (McFarland et al., 2018; Tshemiak et al., 2017), a database to assess the functional requirements of genes across 717 cancer cell lines using CRISPR technology, discovered that Rb-deficiency and high CDKN2A were associated with higher vulnerability to CDK2 or Cyclin El inhibition (Erik S. Knudsen et al. Cell Reports March 1, 2022, 38: 110448). It was proposed that CDK2 / Cyclin El drives the phosphorylation of pl30 to enable cell-cycle progression in this Rb-deficient CDK2 / Cyclin El-dependent setting.Furthermore, CDK2 / cyclin E phosphorylates oncogenic Myc to oppose ras-induced senescence, highlighting the importance of CDK2 in myc / ras-induced tumorigenesis. (See Per Hydbring, PNAS January 5, 2010, 107 (1) 58-63; Campaner, S., Doni, M., Hydbring, P. et al. Nat Cell Biol 12, 54-59 (2010).) Inactivation of CDK2 has been shown to be synthetically lethal to myc over-expressing cancer cells. See Jan J. Molenaar, PNAS August 4, 2009 106 (31) 12968- 12973; Sara Bolin et al., Oncogene 37: 2850-2862 (2018).)Centrosomal protein CPI 10 plays an important role in centrosome duplicati on / separati on and requires CDK2 phosphorylation to induce centrosome clustering (reviewed in M Kawakami et al., (2018) Mol Cancer Ther 17(4):724-731). Aneuploidy cancer cells are genetically unstable and often have supernumerary centrosomes. If centrosome clustering is blocked, aneuploid cells with supernumerary centrosomes undergo multipolar division, leading to apoptosis of daughter cells, a process called anaphase catastrophe. In addition, CPI 10 is downregulated in KRAS-mutant lung cancer, enhancing sensitivity of this cancer to CDK2 inhibitors. In models of KRAS-mutant lung cancer, CDK2 inhibition resulted in anaphase catastrophe and apoptosis and reduced growth of lung cancer xenografts. Because aneuploid cells with supernumerary centrosomes occur in many cancers, there might be potential to extend CDK2 inhibitors to other settings beyond KRAS- mutant lung cancer.CDK2 was also shown to play a role in blocking myeloid differentiation in AML. (Meidan Ying et al., Blood 2018 Jun 14;131(24):2698-2711.) Inhibiting CDK2 effectively induced granulocytic differentiation in AML cell lines and arrested tumor growth in AML mice models.Synergetic effect was demonstrated for combining CDK2 inhibition and all-trans-retinoic acid (ATRA) in AML both in vitro and in vivo. (See Xuejing Shao et al., Pharmacol Res., 2020 151 : 104545.)Pharmacologic inhibition or genetic deletion of CDK2 has also been shown to preserve hearing function in animal models treated with cisplatin or noise (see Teitz T et al. J Exp Med. 2018 Apr 2;215(4): 1187-1203). Therefore, in addition to anti-tumor therapies, CDK2 inhibition can also be used as a promising preventive treatment for noise-, cisplatin-, or antibiotic-induced or age-related hearing loss, for which no Food and Drug Administration approved drugs are currently available.Given the role of CDK2 in human malignancy, there is a need for CDK2 inhibitors for the treatment of cancers and related diseases. The present disclosure fulfills this and related needs.SummaryIn a first aspect, provided is a method of treating a disease treatable by inhibition of CDK2 comprising administering to the patient in need thereof a compound of Formula (I):wherein:W is N, CH, or C when attached to R4;X and Z are independently CR6, NR7, N, O, or S; and Y is CR8, NR9, or N; provided that both of X and Z are not simultaneously O or S; and when each of X and Z is CR6, then Y is other than CR8; each R6is independently hydrogen, alkyl, halo, hydroxyalkyl, or cyano;R7is hydrogen or alkyl;R8and R9are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, wherein:(A) cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one or two Raindependently selected from hydrogen, deuterium, alkyl, deuteroalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, alkylamino, and dialkylamino;(B) heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8and R9are substituted with Rb, Rc, and Rdindependently selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl (wherein cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl are substituted with one or two substituents independently selected from hydrogen, alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, hydroxy, cyano, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, heteroaryl, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl are substituted with Re, Rf, and Rgindependently selected from hydrogen, alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, amino, alkylamino, and dialkylamino); and(C) aryl, by itself or as part of aralkyl, and heteroaryl, by itself or as part of heteroaralkyl, of R8and R9are substituted with Rh, R1, and Rkindependently selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl (wherein cycloalkyl is optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, hydroxy, cyano, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, heteroaryl, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl are substituted with Rm, Rn, and R° independently selected from hydrogen, alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, amino, alkylamino, and dialkylamino); ring RDis phenyl or heteroaryl;R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or cyano;Ar1is cycloalkyl, cycloalkylalkyl, fused cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, bicyclic heterocyclyl, bicyclic heterocyclylalkyl, bridged heterocyclyl, bridged heterocyclylalkyl, fused heterocyclyl, fused heterocyclylalkyl, spiro heterocyclyl, and spiro heterocyclylalkyl (wherein cycloalkyl, by itself or as part of cycloalkylalkyl, fused cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, byitself or as part of bicyclic heterocyclylalkyl, bridged heterocyclyl, by itself or as part of bridged heterocyclylalkyl, fused heterocyclyl, by itself or as part of fused heterocyclylalkyl, and spiro heterocyclyl, by itself or as part of spiro heterocyclylalkyl, are substituted with Rp, Rq, and Rrindependently selected from hydrogen, alkyl, alkoxy, alkylsulfonyl, alkyloxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano)); provided that heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, or spiro heterocyclyl substituted with Rp, Rq, and Rris attached to the -SO2- of -NHSO2- via a carbon ring atom;R4is hydrogen, alkyl, cycloalkyl, cyano, amino, halo, or haloalkyl;R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, heterocyclyl, bicyclic heterocyclyl, fused heterocyclyl, fused heteroaryl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, heteroaryl, or fused heteroaryl wherein: each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, wherein each of the aforementioned ring is substituted with Rvand Rwindependently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, and cyano; each of n1, n2, n3, n4, n5, n6, and n7is 0 or 1, provided that, when Q is a bond, then each of n1, n2, n3, n4, n5, n6, and n7is 1; each alk1, alk2, alk3, alk4, alk5, alk6, and alk7is alkylene;R11, R18, and R20are hydrogen or alkyl;R10, R12, R15, R19, and R21are independently selected from hydrogen, alkyl, fluoro, chloro, bromo, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fusedheterocyclyl, spiro heterocyclyl, heterocyclylalkyl, and -CR22=CR23R24[where R22is hydrogen, alkyl, or cyano, R23is hydrogen or alkyl, and R24is hydrogen, alkyl, halo, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, alkylamino, dialkylamino, -(alkylene)-NR25R26(where R25and R26are independently hydrogen, or alkyl), or heterocyclylalkyl], wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, and spiro heterocyclyl of R10, R12, R15, R19, and R21and heterocyclyl of heterocyclylalkyl of R24are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl; provided R10, R15, R29, and R21are not hydrogen;R13, R14, R16, and R17are independently selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl, wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl, by itself or as part heterocyclylalkyl, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano; and the heterocyclyl, bicyclic heterocyclyl, fused heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro cyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryloxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); or a pharmaceutically acceptable salt thereof.In a second aspect, provided is a compound of Formula (II):wherein:W, X, Y, Z, RD, R1, R2, R3, R4, R5, and Ar1are as defined in the first aspect.In a third aspect, provided is a compound of according to Formula (IIA):wherein:R8is hydrogen, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, wherein:(A) cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8are substituted with one or two Rawhere Rais as defined in the compound of Formula (I);(B) heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8are substituted with Rb, Rc, and Rdwhere Rb, Rc, and Rdare as defined in the compound of Formula (I); and(C) aryl, by itself or as part of aralkyl, and heteroaryl, by itself or as part of heteroaralkyl, of R8are substituted with Rh, R', and Rkwhere Rh, R', and Rkare as defined in the compound of Formula (I) ;R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, heterocyclyl, bicyclic heterocyclyl, fused heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, heteroaryl, or fused heteroaryl; where Q, Q1, Q2, Q3, Q4, Q5, Q6; n1, n2, n3, n4, n5, n6, n7; alk1, alk2, alk3, alk4, alk5, alk6, alk7; R11,R18, and R20; R10, R12, R15, R19, and R21; R11, R18, and R20; R10, R12, R15, R19, and R21are as defined in the compound of Formula (I); and wherein: the heterocyclyl, bicyclic heterocyclyl, fused heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro cyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, and heterocyclyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part of heteroaryloxy and heteroaralkyl, and heterocyclyl as part of heterocyclyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); and the remaining groups in Formula (IIA) are as defined in the compound of Formula (I); or a pharmaceutically acceptable salt thereof; provided that compound of Formula (IIA) is notare as listed in the table below:In an embodiment of the third aspect (herein may be referred to as a fourth aspect), the compound of Formula (IIA) is according to Formula (IIB):wherein:R8is hydrogen, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl other than morpholinyl, tetrahydropyranyl, or pyrrolidinyl, bicyclic heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl, wherein:(A) cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8are substituted with Rawhere Rais as defined in the compound of Formula (I); (B) heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8are substituted with Rb, Rc, and Rdwhere Rb, Rc, and Rdare as defined in the compound of Formula (I);R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, or fused heteroaryl where Q, Q1, Q2, Q3, Q4, Q5, Q6; n1, n2, n3, n4, n5, n6, n7; alk1, alk2, alk3, alk4, alk5, alk6, alk7; R11, R18, and R20; R10, R12, R15, R19, and R21; R11, R18, and R20; R10, R12, R15, R19, and R21as defined in the compound of Formula (I); and wherein: the cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, spiro cyclylsulfoximinyl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); and the remaining groups in Formula (IIB) are as defined in the compound of Formula (I); or a pharmaceutically acceptable salt thereof; provided that the compound of Formulaare as listed in the table below:In a fifth aspect, provided is a compound of Formula (IIC):wherein:R8is alkyl;R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, or fused heteroaryl where Q, Q1, Q2, Q3, Q4, Q5, Q6; n1, n2, n3, n4, n5, n6, n7; alk1, alk2, alk3, alk4, alk5, alk6, alk7; R11, R18, and R20; R10, R12, R15, R19, and R21; R11, R18, and R20; R10, R12, R15, R19, and R21are as defined in the compound of Formula (I) and wherein: the cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl,aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaryloxy, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); and the remaining groups in Formula (IIC) are as defined in the compound of Formula (I); or a pharmaceutically acceptable salt thereof; provided that the compound of Formula (IIC) is notare as listed in the table below:In an embodiment of the fifth aspect, the compound of Formula (IIC) is according to Formula (IIC 1) wherein:wherein:R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q4- (alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, or fused heteroaryl wherein: each of Q, Q1, Q2, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, wherein each of the aforementioned ring is substituted with Rvand Rwindependently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, and cyano; the cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); or a pharmaceutically acceptable salt thereof; provided the compound of Formula (IIC 1 ) is notare as listed in the table below:In a first embodiment (i.e., of the second, third, fourth, and fifth aspects and embodiment of the fifth aspect, the compounds of Formulae (II), (IIA), (IIB), (IIC), and (IIC 1) are wherehydrogen and Rpand Rqare other than hydrogen.In a second embodiment of first, second, third, fourth, and fifth aspects and embodiment of the fifth aspect, the compounds of Formulae (I), (IIA), (IIB), (IIC), and (IIC 1) is not a compound of Formula (X):wherein:R1is hydrogen or halo;R5is a ring of formula (i), (ii), (iii), or (iv):(i) (ii) ('") (iv) where alk is alkyl and (i) is substituted with Rvand Rwindependently selected from hydrogen, alkyl, and halo and (ii), (iii), and (iv) are substituted with Rxand Ryindependently selected from hydrogen, alkyl, and halo;R8is cycloalkyl, bridged cycloalkyl, heterocyclyl, or bridged heterocyclyl, wherein:(A) cycloalkyl and bridged cycloalkyl of ring R8are substituted with one Raselected from hydrogen, halo, haloalkyl, and hydroxalkyl;(B) heterocyclyl and bridged heterocyclyl wherein heterocyclyl and bridged heterocyclyl of ring R8are substituted with Rb, Rc, and Rdwhere Rband Rcare independently selected from hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkyl, and haloalkoxy and Rdis hydrogen, alkyl, deuteroalkyl, cycloalkyl (optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, or heteroaryl; andRpand Rqare independently selected from hydrogen, alkyl, cycloalkyl, alkoxy, halo, haloalkyl, and haloalkoxy; or a pharmaceutically acceptable salt thereof; and / or a compound disclosed in table X:Table Xwhich are disclosed in PCT application No. PCT / US23 / 64895, filed on March 24th, 2023, the content of which is incorporated herein by reference in its entirety. See also WO 2023 / 192801 at pages 11-18 (Definitions), 18-42 (Table I), 42-57 (Embodiments) and 194 (Claim 1).In a sixth aspect, provided is a pharmaceutical composition comprising a compound of Formula (I), (II), (IIA), (IIB), (IIC), or (IIC 1) (or any of the embodiments thereof described herein), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.In general, compounds of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) selectively inhibit CDK2 over CDK1, CDK4 and / or CDK6. As such, in a seventh aspect, provided is a method of treating a disease treatable by inhibition of CDK2 in a patient, preferably the patient is in need of such treatment, which method comprises administering to the patient, preferably a patient in need of such treatment, a therapeutically effective amount of a compound of Formula (I), (II), (IIA), (IIB), (IIC), or (IIC 1) (or any of the embodiments thereof described herein), or a pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof as disclosed herein.In a first embodiment of the first and seventh aspects, the disease is cancer. In a second embodiment of the first and seventh aspects, the disease is cancer selected from ovarian cancer, endometrial cancer, breast cancer (e.g., hormone receptor-positive breast cancer and triplenegative breast cancer), lung cancer (e.g., adenocarcinoma, small cell lung cancer, non-small cell lung carcinomas, parvicellular and non-parvicellular carcinoma, bronchial carcinoma, bronchial adenoma, and / or pleuropulmonary blastoma), skin cancer (e.g. melanoma, squamous cellcarcinoma, Kaposi sarcoma, and / or Merkel cell skin cancer), bladder cancer, cervical cancer, colorectal cancer, cancer of the small intestine, colon cancer, rectal cancer, cancer of the anus, gastric cancer, head and neck cancer (e.g., cancers of the larynx, hypopharynx, nasopharynx, oropharynx, lips, and / or mouth), liver cancer (e.g., hepatocellular carcinoma or cholangiocellular carcinoma), prostate cancer, testicular cancer, uterine cancer, esophageal cancer, gall bladder cancer, pancreatic cancer (e.g. exocrine pancreatic carcinoma), stomach cancer, thyroid cancer, and parathyroid cancer. In a third embodiment of the first and seventh aspects, the disease is cancer that are resistant to CDK4 / 6 inhibitors through CDK2-mediated mechanisms.In an eighth aspect, provided is a method of treating noise-, cisplatin- or antibiotic- induced- or age-related hearing loss, which method comprises administering to the patient, preferably a patient in need of such treatment, a therapeutically effective amount of a compound of Formula (I), (II), (IIA), (IIB), (IIC) or (IIC 1) (or any of the embodiments thereof described herein), or a pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof as disclosed herein. In some embodiments, the amount of hearing loss is reduced when compared to an age-matched control. In some embodiments, the hearing loss is prevented when compared to an age-matched control.In a ninth aspect, provided is a compound of Formula (I), (II), (IIA), (IIB), (IIC) or (IIC 1) (or any of the embodiments thereof described herein), or a pharmaceutically acceptable salt thereof for use in the treatment of a disease treatable by inhibition of CDK2. In one embodiment of the eighth aspect, the compound Formula (I), (II), (IIA), (IIB), (IIC) or (IIC 1) (and any of the embodiments thereof described herein), or a pharmaceutically acceptable salt thereof is useful for the treatment of one or more of diseases disclosed in the seventh and / or eighth aspects above, including embodiments therein.In a tenth aspect, provided is the use of a compound of Formula (I), (II), (IIA), (IIB), (IIC) or (IIC 1) (and any of the embodiments thereof disclosed herein)), or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a disease in a patient treatable by inhibition of CDK2. In an embodiment of the tenth aspect, the disease is one or more of diseases disclosed in the seventh and / or eighth aspects above (including embodiments therein).In any of the aforementioned aspects involving the treatment of cancer, are further embodiments comprising administering the compound of Formula (I), (II), (IIA), (IIB), (IIC), or (IIC 1 ) (or any of the embodiments thereof disclosed herein), or a pharmaceutically acceptable salt thereof in combination with at least one additional anticancer agent. When combination therapy is used, the agents can be administered simultaneously or sequentially.Detailed DescriptionUnless otherwise stated, the following terms used in the specification and claims are defined for the purposes of this Application and have the following meaning:“Alkyl” means a linear saturated monovalent hydrocarbon radical of one to six carbon atoms or a branched saturated monovalent hydrocarbon radical of three to six carbon atoms, e.g., methyl, ethyl, propyl, 2-propyl, butyl, pentyl, and the like.“Alkylene” means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical of three to six carbon atoms unless otherwise stated, e.g., methylene, ethylene, propylene, 1 -methylpropylene, 2-methylpropylene, butylene, pentylene, and the like.“Alkoxy” means a -OR radical where R is alkyl as defined above, e.g., methoxy, ethoxy, propoxy, or 2-propoxy, n-, iso-, or tert-butoxy, and the like.“Alkoxyalkyl” means a linear monovalent hydrocarbon radical of one to six carbon atoms or a branched monovalent hydrocarbon radical of three to six carbons substituted with one alkoxy group as defined above, e.g., 2-methoxyethyl, 1-, 2-, or 3 -methoxypropyl, 2-ethoxyethyl, and the like.“Alkoxyalkyloxy” means a -ORZwhere Rzis alkoxyalkyl as defined above. Representative examples include, but are not limited to, 2-methoxy ethyloxy, 1-, 2-, or 3- methoxypropyloxy, 2-ethoxyethyl oxy, and the like.“Alkoxyalkyloxyalkyl” means a -(alkylene)-Rzwhere Rzis alkoxyalkyloxy as defined above. Representative examples include, but are not limited to, 2-methoxy ethyloxymethyl, 1-, 2-, or 3 -methoxypropyloxymethyl, 2-ethoxy ethyloxy ethyl, and the like.“Alkoxycarbonyl” or “alkyloxycarbonyl” means a -C(O)ORZradical where Rzis alkyl as defined above, e.g., ethoxycarbonyl, ethoxycarbonyl, and the like.“Alkoxycarbonyloxy” or “alkyloxycarbonyloxy” means a -OC(O)ORZradical where Rzis alkyl as defined above, e.g., ethoxycarbonyloxy, ethoxycarbonyloxy, and the like.“Alkoxycarbonylamino” means a -NHC(O)ORZradical where Rzis alkyl as defined above, e.g., ethoxy carbonylamino, ethoxy carbonylamino, and the like.“Alkoxycarbonylaminoalkyl” means a -(alkylene)-Rzradical where Rzis alkoxy carbonylamino as defined above, e.g., ethoxy carbonylaminomethyl, ethoxycarbonylaminoethyl, and the like.“Alkyl sulfonyl” means a -SChR7radical where Rzis alkyl as defined above, e.g., methylsulfonyl, ethylsulfonyl, and the like.“Alkylsulfonylalkyl” means a linear monovalent hydrocarbon radical of one to six carbon atoms or a branched monovalent hydrocarbon radical of three to six carbons substituted with one alkylsulfonyl group as defined above, e.g., 2-methylsulfonylmethyl, methylsulfonylethyl, 2- ethylsulfonylethyl, and the like.“Amino” means a -NH2.“Alkylamino” means a -NHR where R is alkyl as defined above e.g., methylamino, ethylamino, propylamino, and the like.“Aminoalkyl” means a linear monovalent hydrocarbon radical of one to six carbon atoms or a branched monovalent hydrocarbon radical of three to six carbons substituted with -NRZ’RZ” where Rz’ and Rz” are independently hydrogen, alkyl, deuteroalkyl, cycloalkyl, cycloalkylalkyl (wherein cycloalkyl and cycloalkyl ring in cycloalkylalkyl are optionally substituted with one, two, or three substituents independently selected from alkyl, haloalkyl, halo, hydroxy, alkoxy, and cyano), haloalkyl, hydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, alkylsulfonylalkyl, alkylcarbonyl, alkoxycarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, each as defined herein. Representative examples include, but are not limited to, aminomethyl, aminoethyl, methylaminomethyl, and the like.“Aminoalkyloxy” or “aminoalkoxy” means a -ORZwhere Rzis aminoalkyl as defined above. Representative examples include, but are not limited to, aminomethyloxy, aminoethyloxy, methylaminomethyloxy, dimetylaminoethyloxy, and the like.“Aminoalkylamino” means a -NR-(alkylene)-NRz’Rz” where R is hydrogen or alkyl and Rz’ and Rz” are independently hydrogen, alkyl, deuteroalkyl, cycloalkyl, cycloalkylalkyl (wherein cycloalkyl and cycloalkyl ring in cycloalkylalkyl is optionally substituted with one, two, or three substituents independently selected from alkyl, haloalkyl, halo, hydroxy, alkoxy, and cyano), haloalkyl, hydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, alkylsulfonylalkyl, alkylcarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, each as defined herein. Representative examples include, but are not limited to, aminoethylamino, methylaminoethyl, diethylaminoethyl, and the like.“Aminocarbonyl” means a -CONRZ’RZ” radical where Rz’ and Rz” are independently hydrogen, alkyl, cycloalkyl (optionally substituted with one, two, or three substituents independently selected from alkyl, halo, hydroxy, alkoxy, or cyano), haloalkyl, hydroxyalkyl, alkoxyalkyl, and alkylcarbonyl, each as defined herein, e.g., aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, and the like.“Aminocarbonylalkyl” means a -(alkylene)-CONRz’Rz” radical where Rz’ and Rz” are independently hydrogen, alkyl, cycloalkyl (optionally substituted with one, two, or three substituents independently selected from alkyl, halo, hydroxy, alkoxy, or cyano), haloalkyl, hydroxyalkyl, alkoxyalkyl, and alkylcarbonyl, each as defined herein.“Acyl” means a -C(O)RZradical where Rzis alkyl, haloalkyl, cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, as defined herein. Representative examples include, but are not limited to, methylcarbonyl, ethyl carbonyl, benzoyl, trifluoromethylcarbonyl, cyclopropylcarbonyl, and the like. When Rzis alkyl, acyl is also referred to herein as alkylcarbonyl.“Aryl” means a monovalent monocyclic or bicyclic aromatic hydrocarbon radical of 6 to 10 ring atoms e.g., phenyl or naphthyl.“Aryloxy” means a -ORZradical where Rzis aryl as defined above. Representative examples include, phenoxy, naphthyloxy.“Aralkyl” means a -(alkylene)-Rzradical where Rzis aryl as defined above. Examples include, but are not limited to, benzyl, phenethyl, and the like.“Bicyclic cycloalkyl” means a saturated monovalent bicyclic hydrocarbon radical of 5 to 10 carbon atoms where the two rings are fused at two adjacent carbon ring atoms. Unless otherwise stated, bicyclic cycloalkyl is optionally substituted with one or two substituents independently selected from deuterium, alkyl, halo, haloalkyl, alkoxy, hydroxy, and cyano. Examples include, but are not limited to, bicyclo[3.1.0]hexan-6-yl, and the like.“Bicyclic heterocyclyl” means a saturated monovalent bicyclic group of 5 to 10 ring atoms where the two rings are fused at two adjacent ring atoms and in which one, two, or three ring atoms are heteroatom independently selected from N, O, and S(O)n, where n is an integer selected from 0 to 2, the remaining ring atoms being C, unless stated otherwise. Additionally, one or two ring carbon atoms of the bicyclic heterocyclyl can optionally be replaced by a -CO- group. The term bicyclic heterocyclyl includes, but is not limited to, 3-azabicyclo[3.1.0]hexan-3-yl, 3- azabicyclo[4.1.0]heptan-3-yl, hexahydrofuro[3,2-b]furanyl, hexahydro-lH-pyrrolizinyl, 3,3- dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, and the like. When bicyclic heterocyclyl contains only nitrogen ring atom(s) it may be referred to herein as bicyclylaminyl and is a subset of bicyclic heterocyclyl.When bicyclic heterocyclyl ring as defined above, contains only -SO2- in the ring, it is also referred to herein “bi cyclyl sulfonyl” and is a subset of the bicyclic heterocyclyl ring.“Bicyclic heterocyclylalkyl” means -(alkylene)-Rzradical where Rzis bicyclic heterocyclyl as defined above.“Bicyclic heterocyclylA” means a saturated monovalent bicyclic group of 5 to 10 ring atoms where the two rings are fused at two adjacent ring atoms and in which one or two ring atoms are heteroatom independently selected from N and O, the remaining ring atoms being C, unless stated otherwise. Additionally, one or two ring carbon atoms of the bicyclic heterocyclyl can optionally be replaced by a -CO- group. The term bicyclic heterocyclylAincludes, but is not limited to, 3-azabicyclo[3.1.0]hexan-6-yl, and the like. When bicyclic heterocyclylAcontains only nitrogen ring atom(s) it may be referred to herein as bicyclylaminylAand is a subset of bicyclic heterocyclylA.“Bicyclylsulfoximinyl” means a saturated monovalent bicyclic ring of 4 to 8 ring atoms where the two rings are fused at two adjacent ring atoms and in which one ring atom is >S(=O)(=NRZ)- where Rzis hydrogen or alkyl, as defined herein, the remaining ring atoms being C. Representative examples of spiro sulfoximinyl include, but is not limited to, l-imino-3- oxohexahydro-3k6-thiobicyclo[3.1.0]hexan-6-yl, and the like.“Bridged cycloalkyl” means a saturated monovalent bicyclic or tricyclic hydrocarbon radical having 5 to 10 ring carbon ring atoms in which one or two ring atoms are linked by a (CRzRzl)n group (where n is an integer selected from 1 to 3 and Rzand Rzlare independently H or methyl) to a non-adjacent ring atom(s) (also may be referred to herein as “bridging” group). For clarity, when the bridged cycloalkyl is a bicyclic ring, it has one bridging group and when the bridged cycloalkyl is a tricyclic ring, it has two bridging groups). Examples include, but are not limited to, bicyclo[l.l. l]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.2]-octyl, adamantyl, and the like.“Bridged heterocyclyl” means a saturated monovalent bicyclic radical having 5 to 9 ring carbon ring atoms in which two non-adjacent ring atoms are linked by a (CRzRzl)n group where n is 1 to 3 and Rzand Rzlare independently H or methyl (also may be referred to herein as “bridging” group) and further wherein one or two ring carbon atoms, including an atom in the bridging group, are replaced by a heteroatom selected from N, O, and S(O)n, where n is an integer selected from 0 to 2. Examples include, but are not limited to, 2-azabicyclo[2.2.1]heptan-2-yl, 3- azabicyclo[3.1.1]-heptan-3-yl, 3-azabicyclo[3.2.1]octan-3-yl, 2-azabicyclo[2.2.2]octyl, quinuclidinyl, 7-oxa-bicyclo[2.2.1]heptyl, and the like.When bridged heterocyclyl contains only nitrogen ring atom(s) it may be referred to herein as bridged cyclylaminyl and is a subset of bridged heterocyclyl.When bridged heterocyclyl ring as defined above, contains only -SO2- in the ring, it is also referred to herein “bridged cyclyl sulfonyl” and is a subset of the bridged heterocyclyl.“Bridged heterocyclylalkyl” means -(alkylene)-R radical where R is bridged heterocyclyl as defined above.“Bridged heterocyclylA” means a saturated monovalent bicyclic radical having 5 to 9 ring carbon ring atoms in which two non-adjacent ring atoms are linked by a (CRzRzl)n group where n is 1 to 3 and Rzand Rzlare independently H or methyl (also may be referred to herein as “bridging” group) and further wherein one or two ring carbon atoms, including an atom in the bridging group, are replaced by a heteroatom selected from N and O. Examples include, but are not limited to, 2-azabicyclo[2.2.2]octyl, quinuclidinyl, 7-oxabicyclo[2.2.1]heptyl, 6- azabicyclo[3.1.1]heptan-3-yl, 8-azabicyclo[3.2.1]octan-3-yl, 2-azabicyclo[2.2.1]heptan-2-yl, 3- azabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-3-yl, and the like.When bridged heterocyclylAcontains only nitrogen ring atom(s) it may be referred to herein as bridged cyclylaminylAand is a subset of bridged heterocyclylA.“Cycloalkyl” means a monocyclic saturated monovalent hydrocarbon radical of three to ten carbon atoms. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.“Cycloalkoxy” means a -ORZradical where Rzis cycloalkyl as defined above. Representative examples include, but are not limited to, cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, and the like.“Cycloalkylalkyl” means an -(alkylene)-Rzradical where Rzis cycloalkyl as defined above. Examples include, but are not limited to, cyclopropylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, and the like.“Cyanoalkyl” means a linear monovalent hydrocarbon radical of one to six carbon atoms or a branched monovalent hydrocarbon radical of three to six carbons substituted with cyano e.g., cyanomethyl, cyanoethyl, and the like.“Cyanoalkoxy” means a -ORZradical where Rzis cyanoalkyl as defined above. Representative examples include, but are not limited to, cyanomethoxy, cyanoethoxy, and the like.“Cyclylsulfoximinyl” means a saturated monovalent monocyclic ring of 4 to 8 ring atoms in which one ring atom is >S(=O)(=NRZ) where Rzis hydrogen or alkyl, as defined herein, the remaining ring atoms being C. Representative examples of cyclylsulfoximinyl include, but is not limited to, 1 -imino- 1 -oxohexahydro- Ik6-thiopyran -4-yl, and the like.“Deuterium” means2H or D.“Dialkylamino” means a -NRZRZ’ where Rzand Rz’ are independently alkyl as defined above e.g., dimethylamino, diethylamino, methylpropylamino, and the like.“Deuteroalkyl” mean alkyl as defined above, which is substituted with one, two, or three deuterium e.g., trideuteromethyl.“Fused cycloalkyl” means a three to six membered cycloalkyl, as defined above, where two adjacent carbon atoms of the cycloalkyl are fused to two adjacent ring atoms of phenyl or a five or six membered heteroaryl, as defined herein, unless stated otherwise. The fused cycloalkyl can be attached at any atom of the ring valency permitting. Non limiting examples of the fused cycloalkyl include 4,5,6,7-tetrahydroindazol-5-yl, and the like.“Fused cyclylaminyl” as used herein, means cyclylaminyl as defined herein above where two adjacent ring atoms of cyclylaminyl are fused to two adjacent ring atoms of phenyl or a five or six membered heteroaryl, each as defined herein, unless stated otherwise. The fused cyclylaminyl can be attached at any atom of the ring. Non limiting examples of the fused cyclylaminyl include indolin-2-one-l-yl, indolinyl, isoindolyl, and the like.“Fused heteroaryl” as used herein, means 5 or 6 membered heteroaryl as defined herein below where two adjacent ring atoms of the 5 or 6 membered heteroaryl are fused to two adjacent ring atoms of 5 to 7 membered cycloalkyl, as defined herein, unless stated otherwise. The fused heteroaryl can be attached at any atom of the ring. Non limiting examples of the fused heteroaryl include 4,5,6,7-tetrahydro-lH-indole, 4,5,6,7-tetrahydro-lH-pyrazole, and the like.“Fused heterocyclyl” as used herein, means heterocyclyl as defined herein below where two adjacent ring atoms of heterocyclyl are fused to two adjacent ring atoms of phenyl or five or six membered heteroaryl, each as defined herein, unless stated otherwise. The fused heterocyclyl can be attached at any atom of the ring. Non limiting examples of the fused heterocycloalkyl include 2,3-dihydrobenzo[b][l,4]-dioxinyl, 2-oxabicyclo[3.1.0]hexanyl, indolin-2-one-l-yl, indolinyl, isoindolyl, and the like.When fused heterocyclyl contains only nitrogen ring atom(s) it may be referred to herein as fused cyclylaminyl and is a subset of fused heterocyclyl.“Fused heterocyclylalkyl” means -(alkylene)-R radical where R is fused heterocyclyl as defined above.“Fused heterocyclylA” as used herein, means heterocyclylAas defined herein below where two adjacent ring atoms of heterocyclylAare fused to two adjacent ring atoms of phenyl or five or six membered heteroaryl, each as defined herein, unless stated otherwise. The fused heterocyclylAcan be attached at any atom of the ring. Non limiting examples of the fused heterocyclylAinclude 2,3-dihydrobenzo[b][l,4]-dioxinyl, 2-oxabicyclo[3.1.0]hexanyl, indolin-2-one-l-yl, indolinyl, isoindolyl, and the like.When fused heterocyclylAcontains only nitrogen ring atom(s) it may be referred to herein as fused cyclylaminylAand is a subset of fused heterocyclylA.“Halo” means fluoro, chloro, bromo, or iodo, preferably fluoro or chloro.“Haloalkyl” means alkyl radical as defined above, which is substituted with one or more halogen atoms, e.g., one to five halogen atoms, such as fluorine or chlorine, including those substituted with different halogens, e.g., -CH2CI, -CF3, -CHF2, -CH2CF3, -CF2CF3, -CF(CH3)2, and the like. When the alkyl is substituted with only fluoro, it can be referred to in this Application as fluoroalkyl.“Haloalkoxy” means a -OR radical where R is haloalkyl as defined above e.g., -OCF3, - OCHF2, and the like. When R is haloalkyl where the alkyl is substituted with only fluoro, it is referred to in this Application as fluoroalkoxy.“Hydroxyalkyl” means a linear monovalent hydrocarbon radical of one to six carbon atoms or a branched monovalent hydrocarbon radical of three to six carbons substituted with one or two hydroxy groups, provided that if two hydroxy groups are present, they are both not on the same carbon atom. Representative examples include, but are not limited to, hydroxymethyl, 2- hydroxy-ethyl, 2-hydroxypropyl, 3 -hydroxypropyl, l-(hydroxymethyl)-2-methylpropyl, 2- hydroxybutyl, 3 -hydroxybutyl, 4-hydroxybutyl, 2,3 -dihydroxypropyl, l-(hydroxymethyl)-2- hydroxyethyl, 2,3-dihydroxybutyl, 3,4-dihydroxybutyl and 2-(hydroxymethyl)-3-hydroxypropyl, preferably 2-hydroxyethyl, 2,3-dihydroxypropyl, and l-(hydroxymethyl)-2 -hydroxy ethyl.“Hydroxyalkyloxy” means a -ORZwhere Rzis hydroxyalkyl as defined above. Representative examples include, but are not limited to, 2-hy doxy ethyloxy, 1-, 2-, or 3- hydroxypropyloxy, 2-hydroxyethyloxy, and the like.“Heteroaryl” means a monovalent monocyclic or fused bicyclic aromatic radical of 5 to 10 ring atoms, unless otherwise stated, where one or more, (in one embodiment, one, two, or three), ring atoms are heteroatom selected from N, O, and S, the remaining ring atoms being carbon. Representative examples include, but are not limited to, pyrrolyl, thienyl, thiazolyl, imidazolyl, furanyl, indolyl, isoindolyl, oxazolyl, isoxazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl, tetrazolyl, and the like. As defined herein, the terms “heteroaryl” and “aryl” are mutually exclusive. When the heteroaryl ring is a monocyclic ring of 5- or 6 ring atoms, it is also referred to herein as 5-or 6-membered monocyclic heteroaryl. When the heteroaryl is bicyclic ring containing 9- or 10 ring atoms, it is also referred to herein as 9-or 10-membered bicyclic heteroaryl.“Heteroaryl oxy” means a -ORZradical where Rzis heteroaryl as defined above. Representative examples include, but are not limited to, pyridinyloxy, imidazolyloxy, pyrimidinyloxy, fuanyloxy, benzimidazolyloxy, and the like.“Heteroaralkyl” means a -(alkylene)-Rzradical where Rzis heteroaryl as defined above, e.g., pyridinylmethyl, and the like. When the heteroaryl ring in heteroaralkyl contains 5- or 6 ring atoms it is also referred to herein as 5-or 6-membered heteroaralkyl.“Heterocyclyl” means a saturated monovalent monocyclic radical of 4 to 8 ring atoms in which one or two ring atoms are heteroatom independently selected from N, O, and S(O)n, where n is an integer from 0 to 2, the remaining ring atoms being C, unless stated otherwise. Additionally, one or two ring carbon atoms in the heterocyclyl ring can optionally be replaced by a -C(=O)- group. The heterocyclyl can be attached at any atom of the ring, valency permitting. More specifically the term heterocyclyl includes, but is not limited to, oxetanyl, pyrrolidinyl, piperidinyl, homopiperidinyl, 2-oxopyrrolidinyl, 2-oxopiperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, thiomorpholinyl, and the like.When heterocyclyl ring as defined above, contains only -SO2- in the ring, it is also referred to herein “cyclylsulfonyl” and is a subset of the heterocyclyl group.“Heterocyclyloxy” means a -ORZradical where Rzis heterocyclyl as defined above. Representive examples include, but are not limited to, oxetanyloxy, piperidinyloxy, pyrrolidinyloxy, tetrahydrofuranyloxy, and the like.“Heterocyclylalkyl” means a -(alkylene)-Rzradical where Rzis heterocyclyl as defined above. Representive examples include, but are not limited to, oxetanylmethyl, piperidinylmethyl, pyrrolidinylethyl, tetrahydrofuranylmethyl, and the like.“Heterocyclylalkyloxy” means a -ORZradical where Rzis hetereocyclylalkyl as defined above. Representive examples include, but are not limited to, oxetanylmethyl oxy, piperidinylmethyloxy, pyrrolidinylethyloxy, tetrahydrofuranylmethyl oxy, and the like.“HeterocyclylA” means a saturated monovalent monocyclic radical of 4 to 8 ring atoms in which one or two ring atoms are heteroatom independently selected from N and O, the remaining ring atoms being C, unless stated otherwise. Additionally, one or two ring carbon atoms in the heterocyclyl ring can optionally be replaced by a -C(=O)- group. More specifically the term heterocyclylAincludes, but is not limited to, pyrrolidinyl, piperidinyl, homopiperidinyl, 2- oxopyrrolidinyl, 2-oxopiperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, and the like. When heterocyclylAcontains only nitrogen ring atom(s) it may be referred to herein as cyclylaminylAand the group is a subset of heterocyclylA.The term “oxo,” as used herein, alone or in combination, refers to =(O).“Optionally substituted aryl” means aryl as defined above, that is optionally substituted with one, two, or three substituents independently selected from alkyl, hydroxyl, cycloalkyl,carboxy, alkoxycarbonyl, hydroxy, alkoxy, alkylsulfonyl, amino, alkylamino, dialkylamino, halo, haloalkyl, haloalkoxy, and cyano.“Optionally substituted aralkyl” means -(alkylene)-Rzwhere Rzis optionally substituted aryl as defined above.“Optionally substituted heteroaryl” means heteroaryl as defined above that is optionally substituted with one, two, or three substituents independently selected from alkyl, alkylsulfonyl, hydroxyl, cycloalkyl, carboxy, alkoxycarbonyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, and cyano.“Optionally substituted heteroaralkyl” means -(alkylene)-Rzwhere Rzis optionally substituted heteroaryl as defined above.“Optionally substituted heterocyclyl” means heterocyclyl as defined above that is optionally substituted with one, two, or three substituents independently selected from alkyl, alkylsulfonyl, alkylcarbonyl, hydroxyl, cycloalkyl, cycloalkylalkyl, carboxy, alkoxycarbonyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, cyanoalkyl, halo, haloalkyl, haloalkoxy, and cyano, unless stated otherwise.“Optionally substituted heterocyclylalkyl” means -(alkylene)-Rzwhere Rzis optionally substituted heterocyclyl as defined above.“Substituted amino” means a -NRZ’RZ” radical where Rz’ is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or alkylcarbonyl and Rz” is cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylcarbonyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, each as defined herein. Representative examples include, but are not limited to, cyclopropylmethylamino, 2-(methylamino)ethylamino, hydroxyethylamino, and the like. When Rz’ is H and Rz” is other than hydrogen, amino may also be referred to herein as monosubstituted amino. When Rz’ and Rz” are other than hydrogen, amino may also be referred to herein as disubstituted amino.“Spiro cycloalkyl” means a saturated bicyclic monovalent hydrocarbon ring having 7 to 11 ring atoms wherein the rings are connected through only one carbon atom, the connecting atom is also called the spiroatom, most often a quaternary carbon (“spiro carbon”). Spiro cycloalkyl is optionally substituted with one or two substituents independently selected from alkyl, halo, alkoxy, hydroxy, and cyano, unless stated otherwise. Representative examples include, but are not limited to, spiro[3,3]hept-2-yl, spiro[3,5]nonan-2-yl, and the like.“Spiro heterocyclyl" means a saturated bicyclic monovalent ring having 6 to 10 ring atoms in which one, two, or three ring atoms are heteroatom selected from N, O, and S(O)n, where n is an integer selected from 0 to 2 inclusive, the remaining ring atoms being C and the rings are connected through only one atom, the connecting atom is also called the spiroatom, most often a quaternary carbon (“spiro carbon”). Spiroheterocyclyl is optionally substituted with one or two substituents independently selected from alkyl, halo, alkoxy, hydroxy, and cyano, unless Representative examples include, but are not limited to, 2,6-diazaspiro-[3.3]heptanyl, 2,2-dioxido- 2-thiaspiro[3 ,3]heptan-6-yl, 2,6-diazaspiro[3 ,4]octanyl, 2-azaspiro[3 ,4]octanyl, 2-azaspiro[3.5]- nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[3.3]heptan-2-yl, 5-azaspiro[2.4]heptan-5-yl, 3- azaspiro[5.5]undecan-3-yl, 8-azaspiro[4.5]decan-8-yl, 6-azaspiro[3.4]octan-6-yl, 2- azaspiro[4.4]nonan-2-yl and the like. When spiro heterocyclyl ring as defined above contains only -SO2- in the ring, it is also referred to herein “spiro sulfonyl” and is a subset of the heterocyclyl group.“Spiro heterocyclylalkyl” means -(alkylene)-Rzradical where Rzis spiro heterocyclyl as defined above.“Spiro heterocyclylA" means a saturated bicyclic monovalent ring having 6 to 10 ring atoms in which one or two ring atoms are heteroatom selected from N and O, the remaining ring atoms being C and the rings are connected through only one atom, the connecting atom is also called the spiroatom, most often a quaternary carbon (“spiro carbon”). Spiro heterocyclylAis optionally substituted with one or two substituents independently selected from alkyl, halo, alkoxy, hydroxy, and cyano, unless otherwise stated. Representative examples include, but are not limited to, 2,6-diazaspiro-[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 2-azaspiro[3.4]octanyl, 2- azaspiro[3.5]-nonanyl, 2,7-diazaspiro[4.4]nonanyl, and the like.When spiro heterocyclylAas defined above, contains only nitrogen atom(s) in the ring, it is also referred to herein spiro cyclylaminylAand it is a subset of the spiro heterocyclylA.“Spiro sulfoximinyl” means a saturated monovalent bicyclic ring of 6 to 12 ring atoms in which one ring atom is >S(=O)(=NRZ)- where Rzis hydrogen or alkyl, as defined herein, the remaining ring atoms being C, and further wherein the two rings are connected through only one atom, the connecting atom is also called the spiroatom, most often a quaternary carbon ("spiro carbon"). Representative examples of spiro sulfoximinyl include, but is not limited to, 2-imino-2- oxo-2^6-thiaspiro[3.3]hepta-6-yl, 2-(2-methylimino)-2-oxo-2k6-thiaspiro[3.3]hepta-6-yl, and the like.The present disclosure also includes protected derivatives of compounds of Formula (I), (IIA), (IIB), (IIC), and (IIC1). For example, when compounds of Formula (I) contain groups suchas hydroxy, carboxy, or any group containing a nitrogen atom(s), these groups can be protected with suitable protecting groups. A comprehensive list of suitable protective groups can be found in T.W. Greene, Protective Groups in Organic Synthesis, 5thEd., John Wiley & Sons, Inc. (2014), the disclosure of which is incorporated herein by reference in its entirety. The protected derivatives of compounds of the present disclosure can be prepared by methods well known in the art.The present disclosure also includes polymorphic forms and deuterated forms of the compound of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1 ) or a pharmaceutically acceptable salt thereof.The term “prodrug” refers to a compound that is made more active in vivo. Certain compounds Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) may also exist as prodrugs, as described in Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology (see Testa, Bernard and Mayer, Joachim M. Wiley-VHCA, Zurich, Switzerland 2003). Prodrugs of the compounds described herein are structurally modified forms of the compound that readily undergo chemical changes under physiological conditions to provide the active compound. Prodrugs are often useful because, in some situations, they may be easier to administer than the compound, or parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not. A wide variety of prodrug derivatives are known in the art, such as those that rely on hydrolytic cleavage or oxidative activation of the prodrug. An example, without limitation, of a prodrug would be a compound which is administered as an ester (the “prodrug”), but then is metabolically hydrolyzed to the carboxylic acid, the active entity. Additional examples include peptidyl derivatives of a compound.A “pharmaceutically acceptable salt” of a compound means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts include: acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as formic acid, acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxy ethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4- toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4’-methylenebis-(3-hydroxy-2- ene-1 -carboxylic acid), 3 -phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid,lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; or salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, tromethamine, N- methylglucamine, and the like. It is understood that the pharmaceutically acceptable salts are nontoxic. Additional information on suitable pharmaceutically acceptable salts can be found in Remington ’s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, PA, 1985, which is incorporated herein by reference in its entirety.The compounds of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) may have asymmetric centers. Compounds of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. Individual stereoisomers of compounds can be synthesized from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art. All chiral, diastereomeric, all mixtures of chiral or diasteromeric forms, and racemic forms are within the scope of this disclosure, unless the specific stereochemistry or isomeric form is specifically indicated. It will also be understood by a person of ordinary skill in the art that when a compound is denoted as (R) stereoisomer, it may contain the corresponding (S) stereoisomer as an impurity and vice versa.Certain compounds of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) can exist as tautomers and / or geometric isomers. All possible tautomers and cis and trans isomers, as individual forms and mixtures thereof are within the scope of this disclosure. Additionally, as used herein the term alkyl includes all the possible isomeric forms of said alkyl group albeit only a few examples are set forth. Furthermore, when the cyclic groups such as aryl is substituted, it includes all the positional isomers albeit only a few examples are set forth. Furthermore, all hydrates of a compound of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) are within the scope of this disclosure.The compounds of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) may also contain unnatural amounts of isotopes at one or more of the atoms that constitute such compounds. Unnatural amounts of an isotope may be defined as ranging from the amount found in nature to an amount 100% of the atom in question, that differ only in the presence of one or more isotopicallyenriched atoms. Exemplary isotopes that can be incorporated into compounds of the present invention, such as a compound of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1) (and any embodiments thereof disclosed herein including specific compounds) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, such as2H,3H,nC,13C,14C,13N,15N,150,17O,18O,32P,33P,35S,18F,36C1,123I, and1251, respectively. Isotopically labeled compounds (e.g., those labeled with3H and14C) can be useful in compound or substrate tissue distribution assays. Tritiated (i.e.,3H) and carbon-14 (i.e.,14C) isotopes can be useful for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e.,2H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements). In some embodiments, in compounds of Formula (I), (II), (IIA), (IIB), (IIC), and (IIC 1), including in Table 1 below one or more hydrogen atoms are replaced by2H or3H, or one or more carbon atoms are replaced by13C- or14C-enriched carbon. Positron emitting isotopes such as150,13N,nC, and15F are useful for positron emission tomography (PET) studies to examine substrate receptor occupancy. Isotopically labeled compounds can generally be prepared by following procedures analogous to those disclosed in the Schemes or in the Examples herein, by substituting an isotopically labeled reagent for a non-isotopically labeled reagent.Certain structures, including Formula (I), (IIA), (IIB), (IIC), and (IIC 1 ) provided herein are drawn with one or more floating substituents i.e., in the structure below, R1, R2, R3and R6are floating substituents. Unless provided otherwise or otherwise clear from the context, the substituent(s) may be present on any atom of the ring to which it is attached, including any ring atom denoted as CH of such ring unless stated otherwise, where chemically feasible and valency rules permitting. For example, in the structure:, the R4substituent can replace any hydrogen on the azabenzo ring, including the hydrogen of CH when W is CH.A “pharmaceutically acceptable carrier or excipient” means a carrier or an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes a carrier or an excipient that is acceptable for veterinary use as well as human pharmaceutical use. “A pharmaceutically acceptablecarrier / excipient” as used in the specification and claims includes both one and more than one such excipient.The term “about,” as used herein, is intended to qualify the numerical values which it modifies, denoting such a value as variable within a margin of error. When no particular margin of error, such as a standard deviation to a mean value given in a chart or table of data, is recited, the term “about” should be understood to mean that range which would encompass ± 10%, preferably ± 5%, the recited value and the range is included.The phrase “optionally” or “optional” as used herein means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, the phrase “cycloalkyl optionally substituted with alkyl” is intended to cover cycloalkyl that is unsubstituted with alkyl and cycloalkyl that is substituted with alkyl.The term “disease” as used herein is intended to be generally synonymous, and is used interchangeably with, the terms “disorder,” “syndrome,” and “condition” (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms, and causes the human or animal to have a reduced duration or quality of life.The term “combination therapy” means the administration of two or more therapeutic agents to treat a disease or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.The term “patient” is generally synonymous with the term “subject” and includes all mammals including humans. Examples of patients include humans, livestock such as cows, goats, sheep, pigs, and rabbits, and companion animals such as dogs, cats, rabbits, and horses. Preferably, the patient is a human.“Treating” or “treatment” of a disease includes:(1) preventing the disease, i.e. causing the clinical symptoms of the disease not to develop in a mammal that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease;(2) inhibiting the disease, i.e., delaying, arresting (i.e., stabilizing), or reducing the development or severity of the disease or its clinical symptoms; or(3) relieving the disease, i.e., causing regression of the disease or its clinical symptoms.In one embodiment, treating or treatment of a disease includes inhibiting the disease, i.e., delaying, arresting or reducing the development or severity of the disease or its clinical symptoms; or relieving the disease, i.e., causing regression of the disease or its clinical symptoms.A “therapeutically effective amount” means the amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof that, when administered to a patient for treating a disease, is sufficient to affect such treatment for the disease. The “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, etc., of the mammal to be treated.The terms "inhibiting" and "reducing," or any variation of these terms in relation to CDK2, includes any measurable decrease or complete inhibition to achieve a desired result. For example, there may be a decrease of about, at most about, or at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or more, or any range derivable therein, reduction of CDK2 activity compared to its normal activity. In some embodiments, the CDK2 activity is reduced by at least 50% as compared to its activity in absence of a treatment described herein. Representative compounds of the disclosure made are disclosed in Table 1 below:Table 1- Ill -Embodiment A: In embodiment A, the present disclosure includes:1. In embodiment 1, provided is a method of treating a disease treatable by inhibition of CDK2 with a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as disclosed in the first aspect in the Summary.2. In embodiment 2, provided is a method of treating a disease treatable by inhibition of CDK2 with a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as disclosed in the first aspect in the Summary wherein the compound of Formula (I) is not a compound of formula (X) as defined in the Summary and / or the compounds in Compound Table X.3. In embodiment 3, the method is as provided in embodiment 1 or 2, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:4. In embodiment 4, the method is as provided in any one of embodiments 1 to 3, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:5. In embodiment 5, the method is as provided in any one of embodiment 1 to 3, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:6. In embodiment 6, the method is as provided in embodiment 5, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where R6is hydrogen, halo, or cyano.7. In embodiment 7, the method is as provided in any one of embodiments 1 to 3 and5, wherein:8. In embodiment 8, the method is as provided in any one of embodiments 1 to 3 and5, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:9. In embodiment 9, the method is as provided in any one of embodiments 1 to 3 and5, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:10. In embodiment 10, the method is as provided in any one of embodiments 1 to 3, 5, and 6, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:11. In embodiment 14, the method is as provided in any one of embodiments 1 to 3, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:12. In embodiment 12, the method is as provided in embodiment 11, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where R6is hydrogen, halo, or cyano.13. In embodiment 13, the method is as provided in any one of embodiments 1 to 3, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where:14. In embodiment 14, the method as provided in of any one of embodiments 1 to 13, is wherein the compound of Formula (I) has a structure according to Formula (la):15. In embodiment 15, the method as provided in any one of embodiments 1 to 14, is wherein the compound of Formulae (I) and (la) has a structure according to Formula (lb):16. In embodiment 16, the method as provided in any one of embodiments 1 to 14, is wherein the compound of Formulae (I) and (la) has a structure according to Formula (Ic):(Ic).17. In embodiment 17, the method as provided in any one of embodiments 1 to 16, is wherein the compound of Formulae (I), (la), and (lb) has a structure according to Formula (Id):(Id).18. In embodiment 18, the method as provided in any one of embodiments 1 to 17, is wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof, has a structure according to Formula (le):(le).19. In embodiment 19, the method is as provided in any one of embodiments 1 to 13, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where ring RDis heteroaryl.20. In embodiment 20, the method is as provided in any one of embodiments 1 to 13 and 19, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof is where ring RDis a six- membered heteroaryl containing one or two nitrogens.21. In embodiment 21, the method is as provided in any one of embodiments 1 to 13, 19, and 20, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof, is wherein ring RDis pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl.22. In embodiment 22, the method as provided in any one of embodiments 1 to 13, and 19 to 21, is wherein the compound of Formula (I) has a structure according to Formulae (If), (Ig), (Ih), (li), (Ij), or (Ik):23. In embodiment 23, the method is as provided in any one of embodiments 1 to 13 and 19, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof, is where ring RDis a bicyclic heteroaryl.24. In embodiment 24, the method as provided any one of embodiments 1 to 13 and 23, is wherein the compound of Formula (I) has a structure according to Formula (Im), (In), (Io), (Ip), or (Iq):25. In embodiment 25, the method is as provided in any one of embodiments 1 to 24, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, or cyano.26. In embodiment 26, the method is as provided in any one of embodiments 1 to 25, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq) or a pharmaceutically acceptable salt thereof, is where R1, R2, and R3are independently hydrogen, deuterium, methyl, ethyl, propyl, fluoro, chloro, bromo, difluoromethyl, trifluorom ethyl, difluorom ethoxy, trifluoromethoxy, methoxy, ethoxy, hydroxy, hydroxymethyl, methoxymethyl, cyano, or -CH2NH2.27. In embodiment 27, the method is as provided in any one of embodiments 1 to 26, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R1, R2, and R3are independently hydrogen, deuterium, methyl, ethyl, propyl, fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, ethoxy, hydroxy, or cyano.28. In embodiment 28, the method is as provided in any one of embodiments 1 to 27, is wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R1and R2are independently hydrogen, deuterium, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, hydroxy, or cyano and R3is hydrogen.29. In embodiment 29, the method is as provided in any one of embodiments 1 to 28, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R1is fluoro, R2is hydrogen, deuterium, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, hydroxy, or cyano and R3is hydrogen.30. In embodiment 30, the method is as provided in any one of embodiments 1 to 29, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R1is fluoro, R2is hydrogen, deuterium, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, or cyano, and R3is hydrogen.31. In embodiment 31, the method is as provided in any one of embodiments 1 to 30, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R1is fluoro and R2and R3are hydrogen.32. In embodiment 32, the method is as provided in any one of embodiments 1 to 31, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is phenyl substituted with Rp, Rq, and Rr. 33. In embodiment 33, the method is as provided in any one of embodiments 1 to 32, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (al), (a2), (a3), (a4), (a5), or (a6) :34. In embodiment 34, the method is as provided in any one of embodiments 1 to 33, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (al).35. In embodiment 35, the method is as provided in any one of embodiments 1 to 33, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (a2).36. In embodiment 36, the method is as provided in any one of embodiments 1 to 33, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (a3).37. In embodiment 37, the method is as provided in any one of embodiments 1 to 33, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (a4).38. In embodiment 38, the method is as provided in any one of embodiments 1 to 33, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (a5).39. In embodiment 39, the method is as provided in any one of embodiments 1 to 33, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where wherein Ar1is a group of formula (a6).40. In embodiment 40, the method is as provided in any one of embodiments 1 to 31, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is heteroaryl substituted with Rp, Rq, and Rr.41. In embodiment 41, the method is as provided in any one of embodiments 1 to 31 and 40, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is five or six membered heteroaryl (for example 2-, 3-, or 4-pyridyl, 2-, 4-, 5-, or 6-pyrimidinyl, 3-, 4-, 5-, or 6-pyridazinyl, 2- or 3-pyrazinyl, 2- or 3-thienyl, 2- or 3-furanyl, 2- or 3- pyrrolyl, or 3-, 4-, or 5-pyrazolyl) substituted with Rp, Rq, and Rr.42. In embodiment 42, the method is as provided in any one of embodiments 1 to 31 and 40, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1isnine or ten membered heteroaryl (for example 2-, 3-, 5-, 6-, 7-, or 8 -benzothienyl, 2-, 3-, 5-, 6-, 7-, or 8 -benzofuranyl, or 2-, 3-, 5-, 6-, 7-, or 8-indolyl) substituted with Rp, Rq, and Rr.43. In embodiment 43, the method is as provided in any one of embodiments 1 to 31, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is cycloalkyl (for example, cyclopropyl, cyclopentyl, or cyclohexyl) substituted with Rp, Rq, and Rr.44. In embodiment 44, the method is as provided in any one of embodiments 1 to 31, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is fused heterocyclyl (for example, 2,3-dihydrobenzofuranyl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-7-yl, or 2, 3, 5, 6, 7, or 8-indolinyl ) substituted with Rp, Rq, and Rr.45. In embodiment 45, the method is as provided in any one of embodiments 1 to 31, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is fused cycloalkyl (for example 4,5,6,7-tetrahydrobenzo[b]thienyl or 2,3-dihydro-lH-indenyl) substituted with Rp, Rq, and Rr.46. In embodiment 46, the method is as provided in any one of embodiments 1 to 45, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rpis hydrogen, halo, haloalkyl, or haloalkoxy.47. In embodiment 47, the method is as provided in any one of embodiments 1 to 46, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rqis hydrogen, alkyl, cycloalkyl, halo, haloalkyl, haloalkoxy, alkoxy, amino, alkylamino, dialkylamino, phenoxy (where phenyl is substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano), aminoalkylamino, and aminoalkoxy.48. In embodiment 48, the method is as provided in any one of embodiments 1 to 47, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rris hydrogen, halo, alkyl, alkoxy, cyano, amino, alkylamino, dialkylamino, cycloalkyl, phenoxy, aminoalkyl, heterocyclyl (substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano), and aminoalkylamino.49. In embodiment 49, the method is as provided in any one of embodiments 1 to 48, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rris hydrogen.50. In embodiment 50, the method is as provided in any one of embodiments 1 to 48, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rris not hydrogen.51. In embodiment 51, the method is as provided in any one of embodiments 1 to 50, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rpis hydrogen.52. In embodiment 52, the method is as provided in any one of embodiments 1 to 50, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rpis other than hydrogen.53. In embodiment 53, the method is as provided in any one of embodiments 1 to 52, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rqis hydrogen.54. In embodiment 54, the method is as provided in any one of embodiments 1 to 52, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rqis other than hydrogen.55. In embodiment 55, the method is as provided in any one of embodiments 1 to 54, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rpis hydrogen, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, or trifluoromethoxy;Rqis hydrogen, fluoro, chloro, methyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, N-methyl,N-dimethylaminoethylamino, 2-dimethylaminoethyloxy, or phenyl oxy; andRris hydrogen, methyl, cyclopropyl, methoxy, fluoro, chloro, bromo, cyano, dimethylamino, ethylamino, diethylamino, ethylmethylamino, isopropylamino, amino, methylamino, phenoxy, cyano, dimethylaminomethyl, methylaminomethyl, l-methylpiperazin-4- yl, morpholin-4-yl, N-methyl, N-dimethylaminoethylamino, or 2-dimethylaminoethyloxy.56a. In embodiment 56a, the method is as provided in any one of embodiments 1 to 55, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im),(In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rpis fluoro, difluoromethyl, difluoromethoxy, or trifluorom ethyl; Rqis fluoro; and Rris hydrogen.56. In embodiment 56, the method is as provided in any one of embodiments 1 to 54, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Ar1is selected from the Ar1groups in compounds listed in Compound Tables 1 and X disclosed herein.57. In embodiment 57, the method is as provided in any one of embodiments 1 to 56, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im),(ln), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where W is N.58. In embodiment 58, the method is as provided in any one of embodiments 1 to 56, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof, is where W is CH or C (when attached to R4)., (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In),(lo), (Ip), and (Iq),59. In embodiment 59, the method is as provided in any one of embodiments 1 to 56 and 58, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R4is hydrogen, fluoro, methyl, cyclopropyl, cyano, difluoromethyl, or trifluoromethyl.59a. In embodiment 59a, the method is as provided in any one of embodiments 1 to 56, 58 and 59, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R4is hydrogen, fluoro, cyano, difluorom ethyl, or trifluoromethyl.59b. In embodiment 59b, the method is as provided in any one of embodiments 1 to 56, and 58 to 59a, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(lj), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R4is hydrogen.60. In embodiment 60, the method is as provided in any one of embodiments 1 to 3 and 13 to 59b, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(lk), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R7is hydrogen.61. In embodiment 61, the method is as provided in any one of embodiments 1 to 3, and 13 to 59b, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R7is alkyl.62. In embodiment 62, the method is as provided in any one of embodiments 1 to 3, and 13 to 59b, and 61, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R7is methyl, ethyl, or propyl.63. In embodiment 63, the method is as provided in any one of embodiments 1 to 3, 5, 6, 10, 11, 12, and 14 to 62, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R6is hydrogen, methyl, ethyl, propyl, fluoro, hydroxymethyl, or cyano.64. In embodiment 64, the method is as provided in any one of embodiments 1 to 3, 5, 6, 10, 11, 12, and 14 to 63, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R6is hydrogen, fluoro, or cyano.65. In embodiment 65, the method is as provided in any one of embodiments 1 to 64, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently alkyl, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl, wherein:(A) cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one or two Ra; and(B) heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8and R9are substituted with Rb, Rc, and Rd.66. In embodiment 66, the method is as provided in any one of embodiments 1 to 65, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are alkyl.67. In embodiment 67, the method is as provided in any one of embodiments 1 to 66, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the alkyl of R8and R9is methyl, ethyl, propyl, or butyl.68. In embodiment 68, the method is as provided in any one of embodiments 1 to 67, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the alkyl of R8and R9is methyl or ethyl.69. In embodiment 69, the method is as provided in any one of embodiments 1 to 67, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im),(In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the alkyl of R8and R9is propyl or butyl.70. In embodiment 70, the method is as provided in any one of embodiments 1 to 67 and 69, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the alkyl of R8and R9is isopropyl, iso-butyl, sec-butyl, or tert-butyl.71. In embodiment 71, the method is as provided in any one of embodiments 1 to 67, 69, and 70, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(lj), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the alkyl of R8and R9is isopropyl or tert-butyl.72. In embodiment 72, the method is as provided in any one of embodiments 1 to 65, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently cycloalkyl, bridged cycloalkyl, or spiro cycloalkyl wherein the cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one or two Ra.73. In embodiment 73, the method is as provided in any one of embodiments 1 to 65 and 72, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(lk), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently cycloalkyl, bridged cycloalkyl, or spiro cycloalkyl wherein the cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one Ra.74. In embodiment 74, the method is as provided in any one of embodiments 1 to 65 and 67 to 73, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the one or two Raare independently selected from hydrogen, deuterium, alkyl, deuteroalkyl, halo, haloalkyl, and cyano.75. In embodiment 75, the method is as provided in any one of embodiments 1 to 65 and 67 to 74, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the one or two Raare independently selected from hydrogen, deuterium, methyl, trideuteromethyl, cyclopropyl, fluoro, chloro, difluoromethyl, trifluoromethyl, hydroxymethyl, cyano, amino, methylamino, diethylamino, and dimethylamino.76. In embodiment 76, the method is as provided in of any one of embodiments 1 to 65 and 67 to 75, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where theone or two Raare independently selected from hydrogen, deuterium, methyl, trideuteromethyl, fluoro, chloro, difluoromethyl, trifluoromethyl, and cyano.77. In embodiment 77, the method is as provided in any one of embodiments 1 to 65 and 72 to 76, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently cycloalkyl and bridged cycloalkyl, each ring is substituted with Raas defined therein.78. In embodiment 78, the method is as provided in any one of embodiments 1 to 65 and 72 to 76, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are spiro cycloalkyl substituted with Raas defined therein.79. In embodiment 79, the method is as provided in any one of embodiments 1 to 65 and 72 to 77, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are cycloalkyl substituted with Raas defined therein.80. In embodiment 80, the method is as provided in any one of embodiments 1 to 65 and 72 to 77, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(lj), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are bridged cycloalkyl substituted with Raas defined therein.81. In embodiment 81, the method is as provided in any one of embodiments 1 to 65, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl wherein the heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8and R9are substituted with Rb, Rc, and Rd.82. In embodiment 82, the method is as provided in any one of embodiments 1 to 65 and 81, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(lk), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently heterocyclyl or bridged heterocyclyl, each ring is substituted with Rb, Rc, and Rd.83. In embodiment 83, the method is as provided in any one of embodiments 1 to 65 and 81, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are spiro heterocyclyl substituted with Rb, Rc, and Rd.84. In embodiment 84, the method is as provided in any one of embodiments 1 to 65, 81, and 82, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are heterocyclyl substituted with Rb, Rc, and Rd.85. In embodiment 85, the method is as provided in any one of embodiments 1 to 65, 81, and 82, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are bridged heterocyclyl substituted with Rb, Rc, and Rd.86. In embodiment 86, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 79 to 82, 84, and 85, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl and bridged cycloalkyl of R8and R9are selected from:and the heterocyclyl and bridged heterocyclyl of R8and R9are selected from:wherein each cycloalkyl and bridged cycloalkyl is substituted with Raas defined therein; and each heterocyclyl and bridged heterocyclyl is substituted with Rb, Rc, and Rd.87. In embodiment 87, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 79 to 82, and 84 to 86, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl and bridged cycloalkyl of R8and R9are selected from:and the heterocyclyl and bridged heterocyclyl of R8and R9are selected from:wherein each cycloalkyl and bridged cycloalkyl is substituted with Raas defined therein; and heterocyclyl and bridged heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.88. In embodiment 88, the method is as provided in any one of embodiments 1 to 65, 67 to 77, and 79, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl of ring R8and R9are selected from:wherein each cycloalkyl is substituted with Raas defined therein.89. In embodiment 89, the method is as provided in any one of embodiments 1 to 65, 72 to 77, 79, 86, 87, and 88, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl of ring R8and R9are selected from:wherein each cycloalkyl is substituted with one or two Raas defined therein.90. In embodiment 90, the method is as provided in any one of embodiments 1 to 65, 67 to 77, and 80, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih),(li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of R8and R9are selected from:wherein each bridged cycloalkyl is substituted with Raas defined therein.91. In embodiment 91, the method is as provided in any one of embodiments 1 to 65,67 to 77, 80, 86, 88, 89, and 90, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le),(If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of R8and R9are selected from: selected from:wherein each bridged cycloalkyl is substituted with Raas defined therein.92. In embodiment 92, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 80, and 86 to 91, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of R8and R9are:and is substituted with Raas defined therein.93. In embodiment 93, the method is as provided in any one of embodiments 1 to 65,67 to 71, 74 to 76, 81, 82, 84, and 88 to 92, wherein the compound of Formulae (I), (la), (lb), (Ic),(Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclyl of R8and R9is selected from:wherein each heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.94. In embodiment 94, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, 81, 82, 84, and 88 to 93, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclyl of R8and R9is selected from:wherein each heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.95. In embodiment 95, the method is as provided in any one of embodiments 1 to 65,67 to 71, 74 to 76, 81, 82, 84, and 86 to 94, wherein the compound of Formulae (I), (la), (lb), (Ic),(Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclyl of R8and R9is selected from:wherein each heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.96. In embodiment 96, the method is as provided in any one of embodiments 1 to 65,67 to 71, 74 to 76, 81, 82, 85, and 88 to 95, wherein the compound of Formulae (I), (la), (lb), (Ic),(Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged heterocyclyl of R8and R9is selected from:wherein each bridged heterocyclyl is substituted with Rb, Rc, and Rd.97 In embodiment 97, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, 81, 82, 85, and 88 to 96, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged heterocyclyl of R8and R9is selected from:wherein each bridged heterocyclyl is substituted with Rb, Rc, and Rdas defined therein98. In embodiment 98, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, 81, 82, 85, and 86 to 97, wherein the compound of Formulae (I), (la), (lb), (Ic),(Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged heterocyclyl of R8and R9is selected from:wherein each bridged heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.99. In embodiment 99, the method is as provided in any one of embodiments 1 to 65, 67 to 75, 77 to 80, and 86 to 98, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais hydrogen, deuterium, chloro, fluoro, difluoromethyl, trifluoromethyl, amino, methylamino, or dimethylamino.100. In embodiment 100, the method is as provided in any one of embodiments 1 to 65, 67 to 80, and 86 to 99, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais hydrogen.101. In embodiment 101, the method is as provided in any one of embodiments 1 to 65, 67 to 80, and 86 to 99, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais fluoro or chloro.102. In embodiment 102, the method is as provided in any one of embodiments 1 to 65, 67 to 80, and 86 to 99, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais difluoromethyl, or trifluoromethyl.103. In embodiment 103, the method is as provided in any one of embodiments 1 to 65, 67 to 74, 77 to 80, and 86 to 98, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais hydrogen or haloalkyl.104. In embodiment 104, the method is as provided in any one of embodiments 1 to 65, 67 to 74, 77 to 80, and 86 to 98, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais hydrogen or halo.105. In embodiment 105, the method is as provided in any one of embodiments 1 to 65, 67 to 74, 77 to 80, and 86 to 98, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le),(If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rais halo or haloalkyl.106. In embodiment 106, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 79, 80, and 86 to 105, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le),(lf), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of R8and R9is bicyclofl .1. l]pentan-l-yl, 3- fluorobicyclofl .1. l]pentan-l-yl, 3-chlorobicyclo-[l .1. l]pentan-l-yl, 3-(hydroxymethyl)- bicyclofl .1. l]pentan-l-yl, 3-(trifluoromethyl)bicyclo[l .1. l]pentan-l-yl, 3-(difluoromethyl)- bicyclo[l.l.l]pentan-l-yl, 3-(methylamino)bicyclo[l.l.l]pentan-l-yl or 3- (dimethylamino)bicyclo[l.l.l]pentan-l-yl and cycloalkyl of R8and R9is cyclobutyl, cyclopropyl, l-(difluoromethyl)cyclobutyl, l-(trifluoromethyl)cyclobutyl, l-(difluoromethyl)cyclopropyl, or 1- (trifluoromethyl)cyclopropyl .107. In embodiment 107, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 80, and 86 to 106, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If),(lg), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of R8and R9is bicyclofl .1. l]pentan-l-yl, 3-fluoro- bicyclofl .1. l]pentan-l-yl, 3 -chlorobicyclofl .1. l]pentan-l-yl, 3-(hydroxymethyl)- bicyclofl .1. l]pentan-l-yl, 3-(trifluoromethyl)bicyclo[l .1. l]pentan-l-yl, 3-(difluoromethyl)- bicyclo[l.l.l]pentan-l-yl, 3-(methylamino)bicyclo[l.l.l]pentan-l-yl or 3- (dimethylamino)bicyclof 1.1.1 ]pentan- 1 -yl .108. In embodiment 108, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 79, and 86 to 106, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl of R8and R9is cyclobutyl, cyclopropyl, 1- (difluoromethyl)cyclobutyl, l-(trifluoromethyl)-cyclobutyl, l-(difluoromethyl)-cyclopropyl, or 1- (trifluoromethyl)cyclopropyl .109. In embodiment 109, the method is as provided in any one of embodiments 1 to 65, 67 to 77, 79, 86 to 106, and 108, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where cycloalkyl of R8and R9is l-(difluoromethyl)cyclobutyl, 1- (trifluoromethyl)cyclobutyl, l-(difluoromethyl)-cyclopropyl, or l-(trifluoromethyl)cyclopropyl.110. In embodiment 110, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, and 81 to 109, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable saltthereof, is where Rband Rcare independently selected from hydrogen, alkyl, halo, haloalkyl, hydroxy, and cyano and Rdis selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl (substituted as defined in the first aspect), haloalkyl, amino, alkylamino, dialkylamino, heterocyclyl, phenyl, phenylalkyl, and heteroaryl wherein phenyl, phenylalkyl, heteroaryl, and heterocyclyl are substituted with Re, Rf, and Rg.111. In embodiment 111, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, and 81 to 110, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rband Rcare independently selected from hydrogen, methyl, fluoro, chloro, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, hydroxy, and cyano, and Rdis selected from hydrogen, methyl, trideuteromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, amino, dimethylamino, diethylamino, 3,3-difluorocyclobutyl, 4,4-difluorocyclohexyl, 3-hydroxy- 3 -methylcyclobutyl, 3 -cyano-3 -methylcyclobutyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydropyran-4-yl, 1 , 1 -di oxidothi etan-3 -yl, 1,1 -dioxidotetrahydro-2H-thiopyran-4-yl, benzyl, phenyl, pyridin-2-yl, pyri din-3 -yl, and pyridin-4-yl.112. In embodiment 112, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, and 81 to 111, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rbis hydrogen, Rcis selected from hydrogen, methyl, fluoro, chloro, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, hydroxy, and cyano, and Rdis selected from hydrogen, methyl, trideuteromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, amino, dimethylamino, diethylamino, 3,3-difluorocyclobutyl, 4,4-difluorocyclohexyl, 3-hydroxy- 3 -methylcyclobutyl, 3 -cyano-3 -methylcyclobutyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydropyran-4-yl, 1 , 1 -di oxidothi etan-3 -yl, 1,1 -dioxidotetrahydro-2H-thiopyran-4-yl, benzyl, phenyl, pyridin-2-yl, pyri din-3 -yl, and pyridin-4-yl.113. In embodiment 113, the method is as provided in any one of embodiments 1 to 65, 67 to 71, 74 to 76, 81, 82, and 84 to 109, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where (i) the heterocyclyl of R8and R9is 3, 5 -dimethylmorpholino, 4- methyltetrahydro-2H-pyran-4-yl, 2,2,4-trimethylpiperazin-l-yl, 4-methylpiperidin-4-yl, 1,4- dimethylpiperidin-4-yl, 3-oxo-8-azabicyclo[3.2.1]octan-8-yl, 2,2-dimethylpyrrolidin-l-yl, 2,2-dimethylazetidin-l-yl, 2,4-dimethylazetidin-l-yl, 2,4,6-trimethylpiperazin-l-yl, 2,6- dimethylpiperazin-l-yl, or 2,5-dimethylpyrrolidin-l-yl; and(ii) the bridged heterocyclyl of R8and R9is 2-oxabicyclo[2.1.1]hexan-l-yl, 7- azabicyclo[2.2.1]heptan-7-yl, 3-oxa-8-azabicyclo[3.2.1]octan-8-yl, 3-methyl-3,8- diazabicyclo[3.2.1]octan-8-yl, 3,3-difluoro-8-azabicyclo[3.2.1]octan-8-yl, 3-(methyl-d3)-3,8- diazabicyclo[3.2.1]octan-8-yl, 3-cyclopropyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(2,2,2- trifluoroethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(2,2-difluoroethyl)-3,8-diazabicyclo[3.2.1]- octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 2-azabicyclo[2.2.2]octan-2-yl, 8- azabicyclo[3.2.1]octan-8-yl, 3-(3,3,3-trifluoropropyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3- azabicyclo[3.2.2]nonan-3-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 8-methyl-3,8- diazabicyclo[3.2.1]octan-3-yl, 3-(dimethylamino)-8-azabicyclo[3.2.1]octan-8-yl, 3-(3,3- difluorocyclobutyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(oxetan-3-yl)-3,8-diazabicyclo-[3.2.1]octan-8-yl, 5-methyl-2,5-diazabicyclo[2.2.2]octan-2-yl, 3 -hydroxy-3 -methyl-8- azabicyclo[3.2. l]octan-8-yl, 3-cyano-3-methyl-8-azabicyclo[3.2. l]octan-8-yl, 3-(4,4-difluoro- cyclohexyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(tetrahydro-2H-pyran-4-yl)-3,8-diazabicyclo-[3.2.1]octan-8-yl, 8-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl, 3-(l,l-dioxidotetrahydro- 2H-thiopyran-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-benzyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-phenyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3- (tetrahydrofuran-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(l,l-dioxidothietan-3-yl)-3,8- diazabicyclo[3.2.1]octan-8-yl, 3-(3-hydroxy-3-methylcyclobutyl)-3,8-diazabicyclo[3.2.1]octan-8- yl, 3,3-dioxido-3-thia-8-azabicyclo[3.2. l]octan-8-yl, 3-(3-cyano-3-methylcyclobutyl)-3,8- diazabicyclo[3.2.1]octan-8-yl, 3-cyclobutyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 2-(l-cyano-7- azabicyclo[2.2.1]heptan-7-yl, 4-(3,3-difluorocyclobutyl)-2,6-dimethylpiperazin-l-yl, 7-methyl-3- oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl, or 3-cyclopropyl-3,8-diazabicyclo[3.2.1]octan-8-yl.114. In embodiment 114, the method is as provided in any one of embodiments 1 to 64, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are independently hydrogen, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, bicyclic cycloalkyl, bicyclic heterocyclyl, spiro heterocyclyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, wherein bicyclic cycloalkyl of R8and R9are substituted with one or two Ra; bicyclic heterocyclyl of R8and R9are substituted with Rb, Rc, and Rdand aryl of R8and R9, by itself or as part of aralkyl, and heteroaryl of R8and R9, by itself or as part of heteroaralkyl, are substituted with Rh, Rj, and Rk.115. In embodiment 115, the method is as provided in any one of embodiments 1 to 64 and 114, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, amino, alkylamino, dialkylamino, substituted amino, phenyl, phenylalkyl, heteroaryl, or heteroaralkyl wherein phenyl and heteroaryl of R8and R9, either by itself or as part of phenylalkyl and heteroaralkyl, respectively, are substituted with Rh, R1, and Rk.116. In embodiment 116, the method is as provided in any one of embodiments 1 to 64, 114, and 115, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R8and R9are 3 -hydroxy- 1,1 -dimethylethyl, 1 -hydroxy- 1 -methylethyl, difluoromethyl, 1 -fluoro- 1- methylethyl, 1 -methoxy- 1 -methylethyl, 1 -cyano- 1 -methylethyl, 12-cyano- 1,1 -dimethylethyl, 1- fluoro-1 -methylethyl, phenyl, 2,6-difluorophenyl, 2, 6-di chlorophenyl, 2-methylphenyl, 2-chloro- 6-fluorophenyl, 2-chlorophenyl, 2-fluorophenyl, 2-methylphenyl, 2-fluoro-6-methylphenyl, pyridin-4-yl, 1 , 1 -dimethyl -2-methylsulfonylethyl, 1 -methyl- 1 -phenylethyl, 1 -methyl- 1 -pyridin-3- ylethyl, amino, methylamino, dimethylamino, diethylamino, N-methyl-N-phenylamino, N-methyl- N-(2-fhrorophenyl)amino, N,N-bis cyclopropylamino, or bicyclo[3.1.0]hexyl.117. In embodiment 117, the method is as provided in any one of embodiments 1 to 116, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q-(alk1)ni- SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15:-Q4-(alk5)n5- CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, or heteroaryl, wherein heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, and heteroaryl are substituted with Rx, Ry, and Ryl.118. In embodiment 118, the method is as provided in any one of embodiments 1 to 117, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q-(alk1)ni- SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15, -Q4-(alk5)n5- CONR16R17, -Q5-(alk6)n6-NR18COR19, or -Q6-(alk7)n7-NR20SO2R21.119. In embodiment 119, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im),(In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q-(alk1)ni- SO2R10.120. In embodiment 120, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q2-(alk3)n3- SO2NR13R14.121. In embodiment 121, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -QJ-(alk2)n2- SO(=NRn)R12.122. In embodiment 122, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q3-(alk4)n4- COR15.123. In embodiment 123, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q4-(alk5)ns- CONR16R17.124. In embodiment 124, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q5-(alk6)n6‘ NR18COR19.125. In embodiment 125, the method is as provided in any one of embodiments 1 to 118, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is -Q6-(alk7)n7- NR20SO2R21.126. In embodiment 126, the method is as provided in any one of embodiments 1 to 125 wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.127. In embodiment 127, the method is as provided in any one of embodiments 1 to 126, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im),(In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, or spiro cycloalkyl, where each of the aforementioned rings is substituted with Rvand Rw.128. In embodiment 128, the method is as provided in any one of embodiments 1 to 127, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl substituted with Rvand Rw.129. In embodiment 129, the method is as provided in any one of embodiments 1 to 127, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is bridged cycloalkyl substituted with Rvand Rw.130. In embodiment 130, the method is as provided in any one of embodiments 1 to 127, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is spiro cycloalkyl substituted with Rvand Rw.131. In embodiment 131, the method is as provided in any one of embodiments 1 to 126, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, or spiro heterocyclylA, where each of the aforementioned rings is substituted with Rvand Rw.132. In embodiment 132, the method is as provided in any one of embodiments 1 to 126 and 131, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is heterocyclylAor bicyclic heterocyclylA, where each of the aforementioned rings is substituted with Rvand Rw.133. In embodiment 133, the method is as provided in any one of embodiments 1 to 126, 131, and 132, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is heterocyclylAsubstituted with Rvand Rw.134. In embodiment 134, the method is as provided in any one of embodiments 1 to 126, 131, and 132, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is bicyclic heterocyclylAsubstituted with Rvand Rw.135. In embodiment 135, the method is as provided in any one of embodiments 1 to 126, and 131, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is bridged heterocyclylAor spiro heterocyclylA, where each of the aforementioned rings is substituted with Rvand Rw.136. In embodiment 136, the method is as provided in any one of embodiments 1 to 126, 131, and 135, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(lj), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is spiro heterocyclylAsubstituted with Rvand Rw.137. In embodiment 137, the method is as provided in any one of embodiments 1 to 126, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is aryl or heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.138. In embodiment 138, the method is as provided in any one of embodiments 1 to 126 and 137, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(lk), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5,and Q6is phenyl or 6 -membered heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.139. In embodiment 139, the method is as provided in any one of embodiments 1 to 126, 137, and 138, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is phenyl substituted with Rvand Rw.140. In embodiment 140, the method is as provided in any one of embodiments 1 to 139, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5,and Q6is other than bond and each of n1, n2, n3, n4, n5, n6, and n7is 0.141. In embodiment 141, the method is as provided in any one of embodiments 1 to 139, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5,and Q6is other than bond and each of n1, n2, n3, n4, n5, n6, and n7is 1.142. In embodiment 142, the method is as provided in any one of embodiments 1 to 139 and 141, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is methylene or ethylene.143. In embodiment 143, the method is as provided in any one of embodiments 1 to 139, 141, and 142, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(lj), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is methylene.144. In embodiment 144, the method is as provided in any one of embodiments 1 to 139 and 141, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(lk), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is ethylene, propylene, butylene, or pentylene.145. In embodiment 145, the method is as provided in any one of embodiments 1 to 139, 141, and 144, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(lj), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is ethylene or butylene.146. In embodiment 146, the method is as provided in any one of embodiments 1 to 117, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein each aforementioned ring is substituted with Rx, Ry, and Ry.147. In embodiment 147, the method is as provided in any one of embodiments 1 to 117 and 146, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(lk), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is heterocyclyl substituted with Rx, Ry, and Ryl.148. In embodiment 148, the method is as provided in any one of embodiments 1 to 117 and 146, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is bicyclic heterocyclyl substituted with Rx, Ry, and Ryl.149. In embodiment 149, the method is as provided in any one of embodiments 1 to 117 and 146, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is spiro heterocyclyl substituted with Rx, Ry, and Ryl.150. In embodiment 150, the method is as provided in any one of embodiments 1 to 117 and 146, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij),(Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is cyclylsulfoximinyl or bicyclylsulfoximinyl, each ring substituted with Rx, Ry, and Ryl.151. In embodiment 151, the method is as provided in any one of embodiments 1 to 117 and 146, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is spiro sulfoximinyl substituted with Rx, Ry, and Ryl.152. In embodiment 152, the method is as provided in any one of embodiments 1 to 117, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is aryl, heteroaryl, or fused heteroaryl, wherein each of the aforementioned ring is substituted with Rx, Ry, and Ryl.153. In embodiment 153, the method is as provided in any one of embodiments 1 to 117, and 152, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is phenyl substituted with Rx, Ry, and Ryl.154. In embodiment 154, the method is as provided in any one of embodiments 1 to 117 and 152, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is 6- membered heteroaryl substituted with Rx, Ry, and Ryl.155. In embodiment 155, the method is as provided in any one of embodiments 1 to 154, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is where:(1) the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are where the:(2) the heterocyclyl, bridged heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, spiro sulfoximinyl, bicyclylsulfoximinyl, cyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:bridged heterocyclyl is:bicyclic heterocyclyl is:spiro heterocyclyl is:spiro sulfoximinyl is:respectively, wherein each ring in (2) is substituted as defined therein; and * wherein in each ring in (1) and (2) above, denotes bond to NH of -NHR5moiety in the method of Formula each ring in (1) denotes bond to remainder of -Q-(alk1)ni- SO2R10, -Q1-(alk2)n12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15, -Q4-(alk5)n5- CONR16R17, -Q5-(alR19, or -Q6-(alk6)n7-NR20SO2R21.156. In embodiment 156, the method is as provided in any one of embodiments 1 to 155, is wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik),(Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is where:(1) the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are where the:IS' IS bridged heterocyclylA' bicyclyl heterocyclylA' fused heterocyclylA IS' spiro heterocyclylrespectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and (2) the heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, bicyclic heterocyclyl, spiro sulfoximinyl, bicyclylsulfoximinyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:heterocyclyl is:bridged heterocyclyl is:bicyclic heterocyclyl is:cyclylsulfoximinyl is:respectively, wherein each ring in (2) is substituted as defined therein; and whereineach ring in (1) and (2) and ' '' in each ring in (1) have the same meaning as in embodiment 155.157. In embodiment 157, the method is as provided in any one of embodiments 1 to 156, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is where:(1) the cycloalkyl, bridged cycloalkyl, heterocyclylA, bicyclic heterocyclylA, spiro heterocyclylA, and arespectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and(2) the heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, spiro sulfoximinyl, bicyclylsulfoximinyl, aryl, and heteroaryl of R5are where:respectively, wherein each ring in (2) is substituted as defined therein; and whereineach ring in (1) and (2); and in each ring in (1) have the same meaning as in embodiment 155 andin each ring in (2) denotes attachment to one of Rx, Ry, and Ryl.158. In embodiment 158, the method is as provided in any one of embodiments 1 to 155, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are:\ * \ respectively, wherein each ring is substituted as defined therein and wherein and in each ring have the same meaning as in embodiment 155.159. In embodiment 159, the method is as provided in any one of embodiments 1 to 155, 156, and 158, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li),(Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are:respectively, where each ring is substituted as defined therein; and whereineach ring have the same meaning as in embodiment 155.160. In embodiment 160, the method is as provided in any one of embodiments 1 to 155, 156, 158, and 159, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl, bridged cycloalkyl, heterocyclylA, bicyclic heterocyclylA, spiro heterocyclylA, and aryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are:respectively, where each ring is substituted as defined therein; and wherein and / nn each ring have the same meaning as in embodiment 155.161. In embodiment 161, the method is as provided in any one of embodiments 1 to 156, 158, and 159, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (H), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl and bridged cycloalkyl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:respectively, and each ring is substituted as defined therein; and wherein-^in each ring have the same meaning as in embodiment 155.162a. In embodiment 162a, the method is as provided in any one of embodiments 1 to 156, 158, 159, and 161, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig),(Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclylAof each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:substituted as defined therein; and wherein and / nn each ring have the same meaning as in embodiment 155.162. In embodiment 162, the method is as provided in any one of embodiments 1 to 156, 158, 161, and 162a, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, iswhere the spiro heterocyclylAof each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:and is substituted as defined therein; and whereineach ring have the same meaning as in embodiment 155.163a. In embodiment 163a, the method is as provided in any one of embodiments 1 to 155, 156, 158, and 161 to 162, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le),(If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bicyclyl heterocyclylAof each Q, Q1, Q2, Q3, Q4, Q5, and Q6is:each ring is substituted as defined therein; and whereineach ring have the same meaning as in embodiment 155.163. In embodiment 163, the method is as provided in any one of embodiments 1 to 155, 156, 158, and 161 to 163a wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If),(Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable saltthereof, is where the aryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:substituted as defined therein; and whereinhave the same meaning as in embodiment 155.164. In embodiment 164, the method is as provided in any one of embodiments 1 to 155, 156, 158, and 161 to 163, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:and is substituted as defined therein; and whereinhave the same meaning as in embodiment 155.165. In embodiment 165, the method is as provided in any one of embodiments 1 to 155, 156, 158, and 161 to 163, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:and is substituted as defined therein; and whereinhave the same meaning as in embodiment 155.166. In embodiment 166, the method is as provided in any one of embodiments 1 to 155 and 158 to 165, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoxaminyl, spiro sulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:heterocyclyl is: spiro heterocyclyl is:bicyclyl sulfoximinyl is: spiro sulfoximinyl is: sed heteroaryl is:respectively, wherein each ring is substituted as defined therein; and wherein in each ring has the same meaning as in embodiment 155. 167a. In embodiment 167a, the method is as provided in any one of embodiments 1 to155 and 158 to 166, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, spiro sulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:respectively, and each ring is substituted as defined therein; and\ * wherein in each ring have the same meaning as in embodiment 155.167. In embodiment 167, the method is as provided in any one of embodiments 1 to 155 and 158 to 166, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, spiro sulfoximinyl, aryl, and heteroaryl, of R5are where:respectively, where each ring is substituted as defined therein; and\ wherein and in each ring have the same meaning as in embodiment 157.168. In embodiment 168, the method is as provided in any one of embodiments 1 to 155 and 158 to 167, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is whereheterocyclyl is: the heterocyclyl of R5is:and have the same meaning as in embodiment 157.169. In embodiment 169, the method is as provided in any one of embodiments 1 to 155 and 158 to 168, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the spiro heterocyclyl,and is substituted as defined therein; and\ * wherein has the same meaning as in embodiment 155.170. In embodiment 170, the method is as provided in any one of embodiments 1 to 155 and 158 to 169, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where bicyclic heterocyclic is: the bicyclic heterocyclyl, of R5is:each ring is substituted as defined therein; ; and whereinin each ring have the same meaning as in embodiment 157.171. In embodiment 171, the method is as provided in any one of embodiments 1 to 155 and 158 to 170, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im p), and (Iq), or a pharmaceutically acceptable salt thereof, is where the aryl of R5is;substituted as defined therein; and\ wherein andhave the same meaning as in embodiment 157.172. In embodiment 172, the method is as provided in any one of embodiments 1 to 155 and 158 to 171, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the bicyclic heterocyclylsubstituted with Rx,Ry, and Ryl; and\ wherein in each ring has the same meaning as in embodiment 155.173. In embodiment 173, the method is as provided in any one of embodiments 1 to 125, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond.174. In embodiment 174, the method is as provided in any one of embodiments 1 to 125 and 173, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of alk2, alk3, alk4, alk5, alk6, and alk7is ethylene, propylene, butylene, or pentylene and each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond.175. In embodiment 175, the method is as provided in any one of embodiments 1 to 125, 173 and 174, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where each of alk2, alk3, alk4, alk5, alk6, and alk7is ethylene or butylene and each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond.176. In embodiment 176, the method is as provided in any one of embodiments 1 to 118, 121, 124, 125 to 145, 155 to 175, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R11, R18, and R20are hydrogen or alkyl (such as methyl, ethyl, or propyl).177. In embodiment 177, the method is as provided in any one of embodiments 1 to 118, 121, 124, 125 to 145, and 155 to 176, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R11, R18, and R20are hydrogen.178. In embodiment 178, the method is as provided in any one of embodiments 1 to 118, 121, 124, 125 to 145, and 155 to 176, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id),(le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R11, R18, and R20are methyl, ethyl, or propyl.179. In embodiment 179, the compound is as provided in any one of embodiments 1 to 145 and 155 to 178, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is whereR15and R19are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, and heterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R10and R21are independently selected from alkyl, cycloalkyl, haloalkyl, fluoro, chloro, - CR22=CR23R24, aryl, aralkyl, heteroaryl, heteroaralkyl, and heterocyclyl wherein cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and heterocyclyl which is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.179-1. In embodiment 179-1, the method is as provided in any one of embodiments 1 to 145 and 155 to 179, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where :R10, R15, R19, and R21are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, and heterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or heterocyclyl which is substituted with one to three substituentsindependently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.179-2. In embodiment 179-2, the compound is as provided in any one of embodiments 1 to 145, and 155 to 179-1, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig)>(lh), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where :R15and R19are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, and heterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R10and R21are independently selected from alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein cycloalkyl, aryl, heteroaryl, and heterocyclyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and heterocyclyl which is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.180. In embodiment 180, the method is as provided in any one of embodiments 1 to 145 and 155 to 179-2, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih),(li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where:R10, R15, R19, and R21are methyl, ethyl, vinyl, fluoro, 2-dimethylaminovinyl, 2- di ethylaminovinyl, 2-diisopropylaminovinyl, l-cyano-2-dimethylaminovinyl, 2- ethylisopropylaminovinyl, l-cyano-2,2-dimethylpropen-l-yl, piperazinyl, 4-methylpiperazinyl, 4- ethylpiperzin-l-yl, 2-m ethoxy ethylpiperazinyl, or morpholin-4-yl;R12is methyl, ethyl, propyl, or vinyl;R13, R14, R16, and R17are independently hydrogen, methyl, ethyl, aminoethyl, methylaminoethyl, dimethylaminoethyl, 2-hydroxy ethyl, di ethylaminoethyl, azeti din-3 -yl, 1- m ethylazeti din-3 -yl, l-ethylazetidin-2-yl, l-methylpyrrolidin-3-yl, l-ethylpyrrolidin-3-yl, 1- methylpiperidinyl, or 1-ethylpiperidinyl.181. In embodiment 181, the method is as provided in any one of embodiments 1 to 119, 126 to 145, and 155 to 180, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If),(Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where the R10is methyl.182. In embodiment 182, the method is as provided in any one of embodiments 1 to 117 and 146 to 181, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rx, Ry, and Rylwhere Rxand Ryare independently selected from hydrogen, deuterium, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, and cyano and Rylis hydrogen, deuterium, alkyl, alkoxy, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl or aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl).183. In embodiment 183, the method is as provided in any one of embodiments 1 to 117 and 146 to 182, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rxand Ryare independently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, and cyano and Rylis hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, aminocarbonyl, aminocarbonylalkyl, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl or aryloxy, heteroaryl, by itself or as part, of heteroaryloxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl).184. In embodiment 184, the method is as provided in any one of embodiments 1 to 117 and 146 to 183, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih),(li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rxand Ryare independently selected from hydrogen, deuterium, and alkyl and Rylis hydrogen heterocyclyl, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy (wherein heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl).185. In embodiment 185, the method is as provided in any one of embodiments 1 to 117 and 146 to 183, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where Rxand Ryare independently selected from hydrogen or methyl and Rylis hydrogen, deuterium, acyl, aminocarbonyl, aminocarbonylalkyl, aminoalkyl, or heterocyclyl wherein heterocyclyl is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, and heterocyclyl. In one embodiment of embodiment 185, Rxand Ryare independently selected from hydrogen and methyl and Rylis hydrogen.186a. In embodiment 186a, the method is as provided in any one of embodiments 1 to 186a, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is 3,3- dioxido-3-thiabicyclo[3.1 ,0]hexan-6-yl, 4-(methylsulfonyl)cyclohexyl, 2,2-dioxidohexahydro-lH- cy cl openta[c]thi ophen-5 -yl, l-(methylsulfonyl)piperidin-4-yl, l-(methylaminosulfonyl)-piperidin- 4-yl, l-(aminosulfonyl)piperidin-4-yl, 4-(piperazin-l-yl)phenyl, 4-methylsulfonylphenyl, 4- dimethylaminom ethylphenyl, 4-(4-methylpiperazin-l-yl)phenyl, 4-(vinylsulfonyl)phenyl, 4- aminosulfonylphenyl, 4-((2-(dimethylamino)vinyl)sulfonyl)phenyl, l-acetylpiperidin-4-yl, 1- fluorosulfonylpiperidin-4-yl, l-acryloylpiperidin-4-yl, 4-(3-(dimethylamino)acryloyl)phenyl, 4- (vinylsulfonimidoyl)phenyl, l-(3-(diethylamino)-acryloyl)piperidin-4-yl, 1 -(3 -(diisopropyl - amino)acryloyl)piperidin-4-yl, 1 -(2-cyano-3 -(dimethylamino)acryloyl)piperidin-4-yl, 4-(2- (diethylamino)vinyl)sulfonylphenyl, 4-((2-(diethylamino)vinyl)sulfonyl)phenyl, 4-((2- (ethyl(isopropyl)amino)vinyl)sulfonyl)phenyl, l-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-4- yl, 4-(2-(diisopropylamino)vinyl)sulfonylphenyl, 4-((l-cyano-2-(dimethylamino)vinyl)sulfonyl)- phenyl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, 1 -(methyl sulfonyl)azepan-4-yl, 2- (methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl, 3-(methylsulfonyl)-3-azabicyclo[3.1 ,0]hexan- 6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6r)-3- (methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 5-(piperazin-l-yl)pyridin-2-yl, 1 -aminosulfonyl -piperi din-4-y 1 , 1 -methylaminosulfonylpiperidin-4-yl, 1 -(4-(2-methoxy ethyl)piperazin- 1 -yl)- piperidin-4-yl, l-dimethylamino-sulfonylpiperidin-4-yl, 4-piperazin-l-ylphenyl, 1 -piperazin- 1- ylsulfonylpiperidin-4-yl, l-(N-(2-dimethylaminoethyl)-N-methylaminosulfonyl)piperidin-4-yl, 1- (N,N-bis-(hydroxyethyl)aminosulfonyl)piperidin-4-yl, l-(4-methylpiperazin-l-ylsulfonyl)- piperidin-4-yl, l-((2-dimethylaminoethylamino)sulfonyl)-piperidin-4-yl, 2-methylsulfonylethyl, 4- (S-methylsulfonimidoyl)cyclohexyl, l-(methylsulfonyl)piperidin-3-yl, 1 -(methyl sulfonyl)-4, 5,6,7- tetrahydro-lH-indazol-5-yl, 3-(methylsulfonyl)propyl, 4-(piperazin-l-ylsulfonyl)cyclohexyl, 1- (N-(l-methylazeti din-3 -yl)-N-methylaminosulfonyl)piperidin-4-yl, l,l-dioxidotetrahydro-2H- thiopyran-4-yl, 2-aminosulfonylethyl, 1 -imino- 1 -oxidohexahydro- 116-thiopyran-4-yl, 2,2-dioxido-2-thiaspiro[3.3]heptan-6-yl, 1 -(methylimino)- 1 -oxidohexahydro- 116-thiopyran-4-yl, 1-(N- (azetidin-3-yl)-N-methylaminosulfonyl)piperidin-4-yl, 2-imino-2-oxido-216-thiaspiro[3.3]heptan- 6-yl, (lR,5S,6s)-3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, (lR,5S,6r)-3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, (4aR,6S)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (3 aR, 5 s,6aS)-2,2- dioxidohexahydro-lH-cyclopenta[c]thiophen-5-yl, l-(methylsulfonylmethyl)-piperidin-4-yl, 7,7- dioxido-7-thiaspiro[3.5]nonan-2-yl, 4-(4-(2-methoxyethyl)piperazin-l-yl)phenyl, 4-(l- methylpiperazin- 1 -yl)phenyl, 5-(piperazin- 1 -yl)pyridin-2-yl, 1 , 1 -di oxidotetrahydrothi ophen-3 -yl,2-fluoro-4-methylsulfonylphenyl, 2-methyl-4-methylsulfonylphenyl, ((lr,3r)-3- (methylsulfonyl)cyclobutyl, 3-((methylsulfonyl)methyl)-bicyclo[l .1. l]pentan-l-yl, 3-(N- methylmethylsulfonamido)bicyclo[l. l.l]pentan-l-yl, 3-((dimethylaminocarbonyl)- methyl)bicyclo[l .1. l]pentan-l-yl, (lr,3r)-3-(N-methylmethylsulfonamido)cyclobutyl, 3- ((methylsulfonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, 3-((N,N-dimethylsulfamoyl)methyl)- bicyclo[l. l.l]pentan-l-yl, 2-(methylimino)-2-oxido-216-thiaspiro[3.3]heptan-6-yl, 3- (sulfamoylmethyl)bicyclo[l .1. l]pentan-l-yl, 3-((S-methylsulfonimidoyl)methyl)- bicyclof 1.1.1 ]pentan- 1 -yl, 1 -aminosulfonylpiperidin-4-yl, 3 -(2-(4-methylpiperazin- 1 -yl)-2- oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 -yl, 3 -(2-(4-,morpholin-4-yl)-2-oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 - yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)-3-fluoro-l-(methylsulfonyl)- piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4-yl.186. In embodiment 186, the method is as provided in any one of embodiments 1 to 185, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is 3,3-dioxido-3-thiabicyclo[3.1.0]-hexan-6-yl, 4-(methylsulfonyl)cyclohexyl, 2,2-dioxidohexahydro-lH- cy cl openta[c]thi ophen-5 -yl, l-(methylsulfonyl)piperidin-4-yl, l-(methylaminosulfonyl)piperidin-4-yl, l-(aminosulfonyl)piperidin-4-yl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 1-acetylpiperidin-4-yl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, l-(methylsulfonyl)azepan-4- yl, 2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl, 3 -(methyl sulfonyl)-3- azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2- (((lR,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, l-aminosulfonylpiperidin-4-yl, 1- methylaminosulfonylpiperidin-4-yl, 1 -dimethylamino-sulfonylpiperidin-4-yl 1 -piperazin- 1 - ylsulfonylpiperidin-4-yl, l-(N-(2-dimethylaminoethyl)-N-methylaminosulfonyl)piperidin-4-yl, 1- (N,N-bis-(hydroxyethyl)aminosulfonyl)piperidin-4-yl, l-(4-methylpiperazin-l-ylsulfonyl)- piperidin-4-yl, l-((2-dimethylaminoethylamino)sulfonyl)-piperidin-4-yl, 2-methylsulfonylethyl, 4- (S-methylsulfonimidoyl)cyclohexyl, l-(methylsulfonyl)piperidin-3-yl, 3-(methylsulfonyl)propyl,1-(N-(l-methylazetidin-3-yl)-N-methylaminosulfonyl)piperidin-4-yl, l,l-dioxidotetrahydro-2H- thiopyran-4-yl, 2-aminosulfonylethyl, 1 -imino- 1 -oxidohexahydro- 116-thiopyran-4-yl, 2,2-dioxido-2-thiaspiro[3.3]heptan-6-yl, 1 -(methylimino)- 1 -oxidohexahydro- 116-thiopyran-4-yl, 1-(N- (azetidin-3-yl)-N-methylaminosulfonyl)piperidin-4-yl, 2-imino-2-oxido-216-thiaspiro[3.3]heptan- 6-yl, (lR,5S,6s)-3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, (lR,5S,6r)-3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, (4aR,6S)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (3 aR, 5 s,6aS)-2,2- dioxidohexahydro-lH-cyclopenta[c]thiophen-5-yl, l-(methylsulfonylmethyl)piperidin-4-yl, 7,7- dioxido-7-thiaspiro[3.5]nonan-2-yl, 1,1 -di oxidotetrahydrothi ophen-3 -yl, 2-fluoro-4- methylsulfonylphenyl, 2-methyl-4-methylsulfonylphenyl, ((lr,3r)-3-(methylsulfonyl)cyclobutyl,3-((methylsulfonyl)methyl)bicyclo[l.l.l]pentan-l-yl, 3-(N-methylmethylsulfonamido)- bicyclofl .1. l]pentan-l-yl, 3-((dimethylaminocarbonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, (lr,3r)- 3-(N-methylmethylsulfonamido)cyclobutyl, 3-((methylsulfonyl)-methyl)bicyclo[l .1. l]pentan-l- yl, 3-((N,N-dimethylsulfamoyl)methyl)-bicyclo[l .1. l]pentan-l-yl, 2-(methylimino)-2-oxido-216- thiaspiro[3.3 ]heptan-6-yl, 3 -(sulfamoylmethyl)bicyclo[ 1.1.1 ]pentan- 1 -yl, 3 -((S- methylsulfonimidoyl)methyl)-bicyclo[l .1. l]pentan-l-yl, l-aminosulfonylpiperidin-4-yl, 3-(2-(4- methylpiperazin- 1 -yl)-2-oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 -yl, 3 -(2-(4-morpholin-4-yl)-2- oxoethyl)bicyclo[l .1. l]-pentan-l-yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)- 3-fluoro-l-(methylsulfonyl)-piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4- yi.187. In embodiment 187, the method is as provided in any one of embodiments 1 to 186, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is 1- (methylsulfonyl)piperidin-4-yl, l-(methylaminosulfonyl)piperidin-4-yl, 1- (aminosulfonyl)piperidin-4-yl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 1-acetylpiperidin-4-yl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, l-(methylsulfonyl)azepan-4- yl, 2-(methylsulfonyl)octahydro-cyclopenta[c]pyrrol-5-yl, 3 -(methyl sulfonyl)-3- azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2- (((lR,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, l-aminosulfonylpiperidin-4-yl, 1- methylaminosulfonylpiperidin-4-yl, 1 -dimethylamino-sulfonylpiperidin-4-yl 1 -piperazin- 1 - ylsulfonylpiperidin-4-yl, l-(N-(2-dimethylaminoethyl)-N-methylaminosulfonyl)piperidin-4-yl, 1- (N,N-bis-(hydroxyethyl)amino-sulfonyl)piperidin-4-yl, l-(4-methylpiperazin-l-ylsulfonyl)- piperidin-4-yl, l-((2-dimethyl-aminoethylamino)sulfonyl)-piperidin-4-yl, 2-methylsulfonylethyl, 4-(S-methylsulfon-imidoyl)cyclohexyl, l-(methylsulfonyl)piperidin-3-yl, 3- (methylsulfonyl)propyl, l-(N-(l-methylazeti din-3 -yl)-N-methylaminosulfonyl)piperidin-4-yl, 1,1- dioxidotetrahydro-2H-thiopyran-4-yl, 2-aminosulfonylethyl, 1 -imino- 1-oxidohexahydro- 116- thiopyran-4-yl, 1 -(methylimino)- 1-oxidohexahydro- 116-thiopyran-4-yl, l-(N-(azeti din-3 -yl)-N- methylaminosulfonyl)piperidin-4-yl, 2-imino-2-oxido-216-thiaspiro[3.3]heptan-6-yl, (4aR,6S)-l,l- dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidooctahydropyridof 1 ,2- b][l,2,6]thiadiazin-6-yl, l-(methylsulfonylmethyl)piperidin-4-yl, 7,7-dioxido-7- thiaspiro[3.5]nonan-2-yl, l,l-dioxido-tetrahydrothiophen-3-yl, 2-fluoro-4-methylsulfonylphenyl,2-methyl-4-methylsulfonylphenyl, ((lr,3r)-3-(methylsulfonyl)cyclobutyl, 3- ((methylsulfonyl)methyl)-bicyclo[l .1. l]pentan-l-yl, 3-(N-methylmethylsulfonamido)- bicyclofl .1. l]pentan-l-yl, 3-((dimethylaminocarbonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, (lr,3r)-3-(N-methylmethyl-sulfonamido)cyclobutyl, 3-((methylsulfonyl)-methyl)bicyclo[l .1. l]pentan-l- yl, 3-((N,N-dimethylsulfamoyl)-methyl)bicyclo[l .1. l]pentan-l-yl, 2-(methylimino)-2-oxido-216- thiaspiro[3.3 ]heptan-6-yl, 3 -(sulfamoylmethyl)bicyclo[ 1.1.1 ]pentan- 1 -yl, 3 -((S- methylsulfonimidoyl)methyl)-bicyclo[l .1. l]pentan-l-yl, l-aminosulfonylpiperidin-4-yl, 3-(2-(4- methylpiperazin- 1 -yl)-2-oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 -yl, 3 -(2-(4-morpholin-4-yl)-2- oxoethyl)bicyclo[l .1. l]-pentan-l-yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)- 3-fluoro-l-(methylsulfonyl)piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4- yi.188. In embodiment 188, the method is as provided in any one of embodiments 1 to 119, 126, 131 to 133, 140, 146, 148, 149, 151, 155 to 160, 162a, 166, 167, 169, 172, and 179 to 187, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is 1- methylsulfonylpiperidin-4-yl, 2-methyl-l-methylsulfonylpiperidin-4-yl, 2,2-dioxido-2- thiaspiro[3.3]heptan-6-yl, 3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, 2,2-dioxidohexahydro-lH- cy cl openta[c]thi ophen-5 -yl, or 2-imino-2-oxido-216-thiaspiro[3.3]heptan-6-yl189. In embodiment 189, the method is as provided in any one of embodiments 1 to 119,126 to 128, 140, 146, 149, 155 to 161, 165 to 167, 169, and 179 to 185 wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula (i) or (ii):(i) (ii) where alk is alkyl and each ring is substituted with Rvand Rw.190. In embodiment 190, the method is as provided in any one of embodiments 1 to 119, 126 to 128, 140, 155 to 161, 165, and 179 to 180, 186a to 187 and 189, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula (i):<i) where alk is alkyl and the ring of formula (i) is substituted with Rvand Rw.191. In embodiment 191, the method is as provided in any one of embodiments 1 to 119, 126 to 128, 140, 155 to 161, 165, and 179 to 180, 186a to 187, 189, and 190, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula (i):<i) where alk is alkyl, Rvis hydrogen, and Rwis fluoro or methyl which is attached at carbon that is meta to the carbon substituted with -SChalk.192. In embodiment 192, the method is as provided in any one of embodiments 1 to 119, 126 to 128, 140, 155 to 161, 165, and 179 to 180, 186a to 187, 189, and 190, wherein thecompound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula (i):where alk is alkyl and Rvand Rware hydrogen. 193. In embodiment 193, the method is as provided in any one of embodiments 1 to 119,126 to 128, 140, 155 to 161, 165, 179 to 180, 186a to 187, 189, 190, and 192, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula:194. In embodiment 194, the method is as provided in any one of embodiments 1 to 117,140, 146, 149, 155 to 157, 166 to 167, 169, and 182 to 189, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula (ii):where the ring of formula (ii) is substituted as defined therein.195. In embodiment 195, the method is as provided in any one of embodiments 1 to 117, 140, 146, 149, 155 to 157, 166 to 167, 169, and 182 to 189, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula:196. In embodiment 196, the method is as provided in any one of embodiments 1 to 117, 140, 146, 148, 155 to 157, 166 to 167, 172, and 182 to 189, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula (iii) or (iv):("0 (iv) where each ring is substituted as defined therein.197. In embodiment 197, the method is as provided in any one of embodiments 1 to 117, 140, 146, 148, 155 to 157, 166 to 167, 172, 182 to 189, and 196, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula:198. In embodiment 198, the method is as provided in any one of embodiments 1 to 119, 126 to 128, 131 to 133, 140, 146, 148, 149, 155 to 162a, 165 to 167, 169, 172, and 179 to 188, wherein the compound of Formulae (I), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is where R5is a ring of formula:199. In embodiment 199, a method disclosed in Table 1, or a pharmaceutically acceptable salt thereof.200. In embodiment 200, the method as disclosed in any one of the embodiments 1 to 199, is wherein the disease is cancer selected from one or more cancers listed in the utility section of this application.Embodiment B:In embodiment B, the present disclosure includes:1A. In embodiment 1A, provided is a compound of Formula (IIA), or a pharmaceutically acceptable salt thereof, as disclosed in the third aspect in the Summary.2A. In embodiment 2A, provided is a compound of Formula (IIB), or a pharmaceutically acceptable salt thereof, as disclosed in the fourth aspect in the Summary.3A. In embodiment 3A, provided is a compound of Formula (IIC), or a pharmaceutically acceptable salt thereof, as disclosed in the fifth aspect in the Summary.4A. In embodiment 4A, provided is a compound of Formula (IIC 1), or a pharmaceutically acceptable salt thereof, as disclosed in an embodiment of the fifth aspect in the Summary.5A. In embodiment 5A, the compound, or a pharmaceutically acceptable salt thereof, is as provided in embodiment 1 A or 2A, wherein the compound of Formulae (IIA) and (IIB) or a pharmaceutically acceptable salt thereof is not a compound of formula (X) or a pharmaceutically acceptable salt thereof as defined in the Summary and / or the compounds in Compound Table X.6A. In embodiment 6A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in embodiment 1 A, 2A, and 5A wherein:7A. In embodiment 7A, the wherein the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, and 6 A, wherein:8 A. In embodiment 8 A, wherein the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in embodiment in any one of embodiments 1 A, 2A, 5A, and 6A, wherein:9A. In embodiment 9A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in embodiment 8A, wherein R6is hydrogen, halo, or cyano.10A. In embodiment 10A, the compound Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6 A, and 8 A, wherein:11 A. In embodiment 11 A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6 A, and 8 A, wherein:12A. In embodiment 12A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A,6 A, and 8 A, wherein:13 A. In embodiment 13 A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6 A, 8 A, and 9 A, wherein:14A. In embodiment 14A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, and 6 A, wherein:15 A. In embodiment 15 A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in embodiment 14A, wherein R6is hydrogen, halo, or cyano.16A. In embodiment 16A, the compound of Formulae (IIA) and (IIB), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, and 6 A, wherein:17A. In embodiment 17A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided in of any one of embodiments 1 A to 16A, wherein the compound of Formulae (IIA), (IIB), (IIC) and (IIC 1), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (la):18A. In embodiment 18A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), and(la), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 17A, wherein the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), and (la), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (lb):19A. In embodiment 19A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), and(la), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to17A, wherein the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), and (la), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (Ic):20A. In embodiment 20A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb) and (Ic), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments lA to 19A, wherein the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), and (Ic), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (Id):21A. In embodiment 21A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), and (Id), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 20 A, wherein the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb),(lc), and (Id), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (le):(le).22A. In embodiment 22A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 16A, wherein ring RDis heteroaryl.23 A. In embodiment 23 A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 16A and 22A, wherein ring RDis a six- membered heteroaryl containing one or two nitrogen. 24A. In embodiment 24A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 16A, 22A, and 23 A, or a pharmaceutically acceptable salt thereof, wherein ring RDis pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl.25A. In embodiment 25A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 16A, and 22A to 24A, wherein the compound of Formula (IIA), (IIB), (IIC), and (IIC 1 ), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (If), (Ig), (Ih), (li), (Ij), or (Ik):26A. In embodiment 26A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 16A and 22A, wherein ring RDis a bicyclic heteroaryl.27A. In embodiment 27A, the compound of Formulae (IIA), (IIB), (IIC), and (IIC 1), or a pharmaceutically acceptable salt thereof, is as provided any one of embodiments 1 A to 16A and 26A, wherein the compound of Formula (IIA), (IIB), (IIC), and (IIC 1 ), or a pharmaceutically acceptable salt thereof, has a structure according to Formula (Im), (In), (Io), (Ip), or (Iq):(for sake of clarity, for purposes of compounds of Formula (IIC) and (IIC 1) in structure (la), (lb),28A. In embodiment 28A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 27A, wherein R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, or cyano.29A. In embodiment 29A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 28A, wherein R1, R2, and R3are independently selected from hydrogen, deuterium, methyl, ethyl, propyl, fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, ethoxy, hydroxy, hydroxymethyl, methoxymethyl, cyano, and - CH2NH2.30A. In embodiment 30A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 29A, wherein R1, R2, and R3are independently hydrogen, deuterium, methyl, ethyl, propyl, fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, ethoxy, hydroxy, or cyano.31 A. In embodiment 31 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 30A, wherein R1and R2are independently hydrogen, deuterium, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, hydroxy, or cyano and R3is hydrogen.32A. In embodiment 32A, the compound Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb),(lc), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 31 A, or a pharmaceutically acceptable salt thereof, wherein R1is fluoro, R2is hydrogen, deuterium, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, hydroxy, or cyano and R3is hydrogen.33A. In embodiment 33A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 32A, wherein R1is fluoro, R2is hydrogen, deuterium, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, or cyano, and R3is hydrogen.34A. In embodiment 34A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 33A, or a pharmaceutically acceptable salt thereof, is wherein R1, R2and R3are hydrogen.35 A. In embodiment 35 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 33A, or a pharmaceutically acceptable salt thereof, is wherein R1is fluoro and R2and R3are hydrogen.36A. In embodiment 36A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 35 A, or a pharmaceutically acceptable salt thereof, wherein Ar1is phenyl substituted with Rp, Rq, and Rr.37 A. In embodiment 37 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 36A, wherein Ar1is a group of formula (al), (a2), (a3), (a4), (a5), or (a6) below:38 A. In embodiment 38 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 37A, wherein Ar1is a group of formula (al).39 A. In embodiment 39 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 37A, wherein Ar1is a group of formula (a2).40 A. In embodiment 40 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 37A, wherein Ar1is a group of formula (a3).41 A. In embodiment 41 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 37A, wherein Ar1is a group of formula (a4).42A. In embodiment 42A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 37A, wherein Ar1is a group of formula (a5).43A. In embodiment 43A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 37A, wherein Ar1is a group of formula (a6).44A. In embodiment 43A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 35A, or a pharmaceutically acceptable salt thereof, wherein Ar1is heteroaryl substituted with Rp, Rq, and Rr.45A. In embodiment 45A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 35A and 44A, or a pharmaceutically acceptable salt thereof, wherein Ar1is five or six membered heteroaryl (for example 2-, 3-, or 4-pyridyl, 2-, 4-, 5-, or 6-pyrimidinyl, 3-, 4-, 5-, or 6-pyridazinyl, 2- or 3- pyrazinyl, 2- or 3-thienyl, 2- or 3-furanyl, 2- or 3- pyrrolyl, or 3-, 4-, or 5-pyrazolyl) substituted with Rp, Rq, and Rr.46A. In embodiment 46A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 35A and 44A, or a pharmaceutically acceptable salt thereof, wherein Ar1is nine or ten membered heteroaryl (for example 2-, 3-, 5-, 6-, 7-, or 8 -benzothienyl, 2-, 3-, 5-, 6-, 7-, or 8 -benzofuranyl, or 2-, 3-, 5-, 6-, 7-, or 8-indolyl) substituted with Rp, Rq, and Rr.47 A. In embodiment 47 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 35A, or a pharmaceutically acceptable salt thereof, wherein Ar1is cycloalkyl (for example, cyclopropyl, cyclopentyl, or cyclohexyl) substituted with Rp, Rq, and Rr.48A. In embodiment 48A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 35A, or a pharmaceutically acceptable salt thereof, wherein Ar1is fused heterocyclyl (for example, 2,3- dihydrobenzofuranyl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-7-yl, or 2, 3, 5, 6, 7, or 8-indolinyl ) substituted with Rp, Rq, and Rr.49A. In embodiment 49A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 35A, or a pharmaceutically acceptable salt thereof, wherein Ar1is fused cycloalkyl (for example 4, 5,6,7- tetrahydrobenzo[b]thienyl or 2,3-dihydro-lH-indenyl) substituted with Rp, Rq, and Rr.50A. In embodiment 50A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 49A, wherein Rpis hydrogen, halo, haloalkyl, or haloalkoxy, provided that when Rpis hydrogen or halo and one of Rqand Rris hydrogen, halo, or alkoxy, then the other of Rqand Rris not hydrogen.51A. In embodiment 51A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 50A, wherein Rqis hydrogen, alkyl, cycloalkyl, halo, haloalkyl, haloalkoxy, alkoxy, amino, alkylamino, dialkylamino, phenoxy (where phenyl is substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano), aminoalkylamino, and aminoalkoxy.52A. In embodiment 52A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1A to 51 A, wherein Rris hydrogen, halo, alkyl, alkoxy, cyano, amino, alkylamino, dialkylamino, cycloalkyl, phenoxy, aminoalkyl, heterocyclyl (substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano), or aminoalkylamino,53A. In embodiment 53A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 52A, wherein Rris hydrogen.54A. In embodiment 54A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 52A, wherein Rris other than hydrogen.55A. In embodiment 55A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 54A, wherein Rpis hydrogen.56A. In embodiment 56A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 54, wherein Rpis other than hydrogen.57A. In embodiment 57A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 56, wherein Rqis hydrogen.58A. In embodiment 58A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 to 52, wherein Rqis other than hydrogen.59A. In embodiment 59A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 58A, wherein Rpis hydrogen, fluoro, chloro, difluoromethyl, trifluoromethyl, difluoromethoxy, or tri fluoromethoxy;Rqis hydrogen, fluoro, chloro, methyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, N-methyl,N-dimethylaminoethylamino, 2-dimethylaminoethyloxy, or phenyl oxy; andRris hydrogen, methyl, cyclopropyl, methoxy, fluoro, chloro, bromo, cyano, dimethylamino, ethylamino, diethylamino, ethylmethylamino, isopropylamino, amino, methylamino, phenoxy, cyano, dimethylaminomethyl, methylaminomethyl, l-methylpiperazin-4- yl, morpholin-4-yl, N-methyl, N-dimethylaminoethylamino, or 2-dimethylaminoethyloxy.60A. In embodiment 60A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 59A, wherein Rpis difluoromethyl, difluoromethoxy, or trifluoromethyl; Rqis fluoro; and Rris hydrogen.61A. In embodiment 61A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 49A, wherein Rpis hydrogen or halo; Rqis hydrogen or halo; and Rris hydrogen.62A. In embodiment 62A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 49A and 61 A, wherein Rpis fluoro; Rqis hydrogen or fluoro; and Rris hydrogen.63A. In embodiment 63A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 49A and 61 A, wherein Rpand Rqare fluoro; and Rris hydrogen.64A. In embodiment 64A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 63 A, wherein Ar1is selected from the Ar1groups in compounds listed in Compound Table 1 and / or Table X disclosed herein.65A. In embodiment 65A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 64A, or a pharmaceutically acceptable salt thereof, wherein W is N.66A. In embodiment 66A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 64A, or a pharmaceutically acceptable salt thereof, wherein W is CH or C (when attached to R4).67A. In embodiment 67A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 64A and 66A, or a pharmaceutically acceptable salt thereof, wherein R4is hydrogen, fluoro, methyl, cyclopropyl, cyano, difluoromethyl, or trifluorom ethyl.68A. In embodiment 68A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 64A and 66A, or a pharmaceutically acceptable salt thereof, wherein R4is hydrogen, fluoro, cyano, difluoromethyl, or trifluorom ethyl.69A. In embodiment 69A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 64A and 66A to 68A, or a pharmaceutically acceptable salt thereof, wherein R4is hydrogen.70A. In embodiment 70A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6 A, and 16A to 69A, or a pharmaceutically acceptable salt thereof, wherein R7is hydrogen.71A. In embodiment 71A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6A, and 16A to 69A, or a pharmaceutically acceptable salt thereof, wherein R7is alkyl.72A. In embodiment 72A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6A, and 16A to 69A, and 71 A, or a pharmaceutically acceptable salt thereof, wherein R7is methyl, ethyl, or propyl.73 A. In embodiment 73 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6A, 8A, 9A, 13A, 14A, and 17A to 72A, or a pharmaceutically acceptable salt thereof, wherein R6is hydrogen, methyl, ethyl, propyl, fluoro, hydroxymethyl, or cyano.74A. In embodiment 74A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A, 6A, 8A, 9A, 13A, 14A, and 17A to 73 A, or a pharmaceutically acceptable salt thereof, wherein R6is hydrogen, fluoro, or cyano.75A. In embodiment 75A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 74A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independently alkyl (for compounds of Formulae (IIC) and (IIC 1) and cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl (for compounds of Formulae (IIA) and (IIB), wherein:(A) cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one or two Ra; and(B) heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8and R9are substituted with Rb, Rc, and Rd.76A. In embodiment 76A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 4B, 17A to 69 A and 75 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are alkyl.77A. In embodiment 77A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 4B, 17A to 69A, 75A, and 76A, or a pharmaceutically acceptable salt thereof, wherein the alkyl of R8and R9is methyl, ethyl, propyl, or butyl.78A. In embodiment 78A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 4B, 17A to 69A, 75A, 76A, and 77A, or a pharmaceutically acceptable salt thereof, wherein the alkyl of R8and R9is methyl or ethyl.79A. In embodiment 79A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 4B, 17A to 69A, 75A, 76A, and 77A, or a pharmaceutically acceptable salt thereof, wherein the alkyl of R8and R9is propyl or butyl.80A. In embodiment 80A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 4B, 17A to 69A, 75A, 76A, 77Aand 79A, or a pharmaceutically acceptable salt thereof, wherein the alkyl of R8and R9is isopropyl, iso-butyl, sec-butyl, or tert-butyl.81A. In embodiment 81A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 4B, 17A to 69A, 75A, 76A,77A, 79A, and 80A, or a pharmaceutically acceptable salt thereof, wherein the alkyl of R8and R9is isopropyl or tert-butyl.82A. In embodiment 82A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independentlycycloalkyl, bridged cycloalkyl, or spiro cycloalkyl wherein the cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one or two Ra.83A. In embodiment 83A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, and 82 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independently cycloalkyl, bridged cycloalkyl, or spiro cycloalkyl wherein the cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one Ra.84A. In embodiment 84A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A, and 83 A, or a pharmaceutically acceptable salt thereof, wherein the one or two Raare independently selected from hydrogen, deuterium, alkyl, deuteroalkyl, halo, haloalkyl, and cyano.85A. In embodiment 85A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A and 82 A to 84 A, or a pharmaceutically acceptable salt thereof, wherein the one or two Raare independently selected from hydrogen, deuterium, methyl, trideuteromethyl, cyclopropyl, fluoro, chloro, difluoromethyl, trifluoromethyl, hydroxymethyl, cyano, amino, methylamino, diethylamino, and dimethylamino.86A. In embodiment 86A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in of any one of embodiments 1 A, 2A, 5A to 75A and 82A to 85A, or a pharmaceutically acceptable salt thereof, wherein the one or two Raare independently selected from hydrogen, deuterium, methyl, trideuteromethyl, fluoro, chloro, difluoromethyl, trifluoromethyl, and cyano.87A. In embodiment 87A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A and 82 A to 86 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independently cycloalkyl and bridged cycloalkyl, each ring is substituted with Raas defined therein.88A. In embodiment 88A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A and 82 A to 86 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are spiro cycloalkyl substituted with Raas defined therein.89A. In embodiment 89A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A and 82 A to 87 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are cycloalkyl substituted with Raas defined therein.90A. In embodiment 90A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A and 82 A to 87 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are bridged cycloalkyl substituted with Raas defined therein.91A. In embodiment 91A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A and 5 A to 75 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independently heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl wherein the heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8and R9are substituted with Rb, Rc, and Rd.92A. In embodiment 92A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, and 91 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independently heterocyclyl or bridged heterocyclyl, each ring is substituted with Rb, Rc, and Rd.93 A. In embodiment 93 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, and 91 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are spiro heterocyclyl substituted with Rb, Rc, and Rd.94A. In embodiment 94A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 91 A, and 92 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are heterocyclyl substituted with Rb, Rc, and Rd.95A. In embodiment 95A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 91 A, and 92 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are bridged heterocyclyl substituted with Rb, Rc, and Rd.96A. In embodiment 96A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to75 A, 82 A to 87 A, 89 A to 92 A, 94 A, and 95 A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and bridged cycloalkyl of R8and R9are selected from:and the heterocyclyl and bridged heterocyclyl of R8and R9are selected from:wherein each cycloalkyl and bridged cycloalkyl is substituted with Raas defined therein; and each heterocyclyl and bridged heterocyclyl is substituted with Rb, Rc, and Rd.97A. In embodiment 97A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 87 A, 89 A to 92 A, and 94 A to 96 A , or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and bridged cycloalkyl of R8and R9are selected from:and the heterocyclyl and bridged heterocyclyl of R8and R9are selected from:wherein each cycloalkyl and bridged cycloalkyl is substituted with Raas defined therein; and heterocyclyl and bridged heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.98A. In embodiment 98A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 87 A, and 89 A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl of ring R8and R9are selected from:wherein each cycloalkyl is substituted with Raas defined therein.99A. In embodiment 99A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 87 A, 89 A, 96 A, 97 A, and 98 A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl of ring R8and R9are selected from:wherein each cycloalkyl is substituted with one or two Raas defined therein.100A. In embodiment 100A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 87 A, and 90 A, or a pharmaceutically acceptable salt thereof, wherein the bridged cycloalkyl of R8and R9are selected from:wherein each bridged cycloalkyl is substituted with Raas defined therein.101A. In embodiment 101A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A to 87A, 90A, 98A, 99A, and 100A, or a pharmaceutically acceptable salt thereof, wherein the bridged cycloalkyl of R8and R9are selected from: selected from:wherein each bridged cycloalkyl is substituted with Raas defined therein.102A. In embodiment 96, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A to 87A, 90 A, and 96 A to 101 A, or a pharmaceutically acceptable salt thereof, wherein the bridged cycloalkyl of R8and R9are:and is substituted with Raas defined therein.103 A. In embodiment 103 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 81 A, 84 A to 86 A, 91 A, 92 A, 94 A, and 98 A to 102 A, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl of R8and R9is selected from:wherein each heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.104A. In embodiment 104A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to75A, 82A to 81 A, 84A to 86A, 91 A, 92A, 94A, 96A, and 98A to 103A , or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl of R8and R9is selected from:wherein each heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.105 A. In embodiment 105 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to75 A, 82 A to 81 A, 84 A to 86 A, 91 A, 92 A, 94 A, 96 A, and 98 A to 104 A , or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl of R8and R9is selected from:wherein each heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.106A. In embodiment 106A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 81 A, 84 A to 86 A, 91 A, 92 A, 95 A, and 98 A to 105 A , or a pharmaceutically acceptable salt thereof, wherein the bridged heterocyclyl of R8and R9is selected from:wherein each bridged heterocyclyl is substituted with Rb, Rc, and Rd.107A. In embodiment 107A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 81 A, 84 A to 86 A, 91 A, 92 A, 95 A, and 98 A to 106 A , or a pharmaceutically acceptable salt thereof, wherein the bridged heterocyclyl of R8and R9is selected from:wherein each bridged heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.108 A. In embodiment 108 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 81 A, 84 A to 86 A, 91 A, 92 A, 95 A to 107 A, or a pharmaceutically acceptable salt thereof, wherein the bridged heterocyclyl of R8and R9is selected from:wherein each bridged heterocyclyl is substituted with Rb, Rc, and Rdas defined therein.109A. In embodiment 109A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A to 80A, and 96A to 108A, or a pharmaceutically acceptable salt thereof, wherein Rais hydrogen, deuterium, chloro, fluoro, difluoromethyl, trifluoromethyl, amino, methylamino, or dimethylamino.110A. In embodiment 110A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A to 80A, and 96A to 109A, or a pharmaceutically acceptable salt thereof, wherein Rais hydrogen.111 A. In embodiment 101, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A to 80A, and 96A to 109A, or a pharmaceutically acceptable salt thereof, wherein Rais fluoro or chloro.112A. In embodiment 112A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A to 80A, and 96A to 109A, or a pharmaceutically acceptable salt thereof, wherein Rais difluoromethyl, or trifluoromethyl.113 A. In embodiment 113 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 84 A, 87 A to 90 A and 96 A to 108 A, or a pharmaceutically acceptable salt thereof, wherein Rais hydrogen or haloalkyl.114A. In embodiment 114A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 84 A, 87 A to 90 A, and 96 A to 108 A , or a pharmaceutically acceptable salt thereof, wherein Rais hydrogen or halo.115A. In embodiment 115A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82 A to 84 A, 87 A to 90 A, and 96 A to 108 A , or a pharmaceutically acceptable salt thereof, wherein Rais halo or haloalkyl.116A. In embodiment 116A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A, 83 A, 87A, 89A, 90A, and 96A to 108A, or a pharmaceutically acceptable salt thereof, wherein the bridged cycloalkyl of R8and R9is bicyclo[l.l. l]pentan-l-yl, 3- fluorobicyclofl .1. l]pentan-l-yl, 3-chlorobicyclo-[l .1. l]pentan-l-yl, 3-(hydroxymethyl)- bicyclofl .1. l]pentan-l-yl, 3-(trifluoromethyl)bicyclo[l .1. l]pentan-l-yl, 3-(difluoromethyl)- bicyclo[l. l.l]pentan-l-yl, 3-(methylamino)bicyclo[l. l.l]pentan-l-yl or 3- (dimethylamino)bicyclo[l.l. l]pentan-l-yl and cycloalkyl of R8and R9is cyclobutyl, cyclopropyl, l-(difluoromethyl)cyclobutyl, l-(trifluoromethyl)cyclobutyl, l-(difluoromethyl)cyclopropyl, or 1- (trifluoromethyl)cyclopropyl .117A. In embodiment 117A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A, 83 A, 87A, 90A, and 96A to 116A , or a pharmaceutically acceptable salt thereof, wherein the bridged cycloalkyl of R8and R9is bicyclofl .1. l]pentan-l-yl, 3-fluoro-bicyclofl .1. l]pentan-l-yl, 3 -chlorobicyclofl .1. l]pentan-l-yl, 3-(hydroxymethyl)- bicyclofl .1. l]pentan-l-yl, 3-(trifluoromethyl)bicyclo[l .1. l]pentan-l-yl, 3-(difluoromethyl)- bicyclo[l. l.l]pentan-l-yl, 3-(methylamino)bicyclo[l. l.l]pentan-l-yl or 3-(dimethylamino)- bicyclof 1.1.1 ]pentan- 1 -yl .118A. In embodiment 118A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 82A, 83 A, 87A, 89A, and 96A 116A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl of R8and R9is cyclobutyl, cyclopropyl, l-(difluoromethyl)cyclobutyl, 1- (trifluoromethyl)-cyclobutyl, l-(difluoromethyl)-cyclopropyl, or l-(trifluoromethyl)cyclopropyl.119A. In embodiment 119A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 82A, 83 A, 87A, 89A, 96A to 118A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl ofR8and R9is l-(difluoromethyl)cyclobutyl, l-(trifluoromethyl)cyclobutyl, 1- (difluoromethyl)-cyclopropyl, or l-(trifluoromethyl)cyclopropyl.120A. In embodiment 120A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 84 A to 86 A, and 91 A to 118A, or a pharmaceutically acceptable salt thereof, wherein Rband Rcare independently selected from hydrogen, alkyl, halo, haloalkyl, hydroxy, and cyano and Rdis selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl (substituted as defined in Formula (IIA) and (IIB)), haloalkyl, amino, alkylamino, dialkylamino, heterocyclyl, phenyl, phenylalkyl, and heteroaryl wherein phenyl, phenylalkyl, heteroaryl, and heterocyclyl are substituted with Re, Rf, and Rg.121A. In embodiment 121A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75 A, 84 A to 86 A, 91 A to 120 A, or a pharmaceutically acceptable salt thereof, wherein Rband Rcare independently selected from hydrogen, methyl, fluoro, chloro, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, hydroxy, and cyano, and Rdis selected from hydrogen, methyl, trideuteromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, amino, dimethylamino, di ethylamino, 3, 3 -difluorocyclobutyl, 4,4-difluorocyclohexyl, 3 -hydroxy-3 -methylcyclobutyl, 3-cyano-3 -methylcyclobutyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydropyran-4-yl, 1,1- di oxidothi etan-3 -yl, l,l-dioxidotetrahydro-2H-thiopyran-4-yl, benzyl, phenyl, pyridin-2-yl, pyri din-3 -yl, and pyridin-4-yl.122A. In embodiment 122A, the compound Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 84A to 86A, 91 A to 121 A, or a pharmaceutically acceptable salt thereof, wherein Rbis hydrogen, Rcis selected from hydrogen, methyl, fluoro, chloro, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, hydroxy, and cyano, and Rdis selected from hydrogen, methyl, trideuteromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, amino, dimethylamino, diethylamino, 3,3- difluorocyclobutyl, 4,4-difluorocyclohexyl, 3 -hydroxy-3 -methylcyclobutyl, 3 -cyano-3 - methylcyclobutyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydropyran -4-yl, 1,1 -di oxidothi etan-3 - yl, l,l-dioxidotetrahydro-2H-thiopyran-4-yl, benzyl, phenyl, pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl.123 A. In embodiment 123 A, the compound Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 75A, 84A to 86A, 91 A, 92 A and 94 A to 119A , or a pharmaceutically acceptable salt thereof, wherein (i) the heterocyclyl of R8and R9is 3, 5 -dimethylmorpholino, 4-methyltetrahydro-2H-pyran-4-yl, 2,2,4- trimethylpiperazin-l-yl, 4-methylpiperidin-4-yl, l,4-dimethylpiperidin-4-yl, 3-oxo-8- azabicyclo[3.2.1]octan-8-yl, 2,2-dimethylpyrrolidin-l-yl, 2,2-dimethylazetidin-l-yl, 2,4- dimethylazetidin-l-yl, 2,4,6-trimethylpiperazin-l-yl, 2,6-dimethylpiperazin-l-yl, or 2,5- dimethylpyrrolidin-l-yl; and(ii) the bridged heterocyclyl of R8and R9is 2-oxabicyclo[2.1.1]hexan-l-yl, 7- azabicyclo[2.2.1]heptan-7-yl, 3-oxa-8-azabicyclo[3.2.1]octan-8-yl, 3-methyl-3,8- diazabicyclo[3.2.1]octan-8-yl, 3,3-difluoro-8-azabicyclo[3.2.1]octan-8-yl, 3-(methyl-d3)-3,8- diazabicyclo[3.2.1]octan-8-yl, 3-cyclopropyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(2,2,2- trifluoroethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(2,2-difhroroethyl)-3,8-diazabicyclo[3.2.1]- octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 2-azabicyclo[2.2.2]octan-2-yl, 8- azabicyclo[3.2.1]octan-8-yl, 3-(3,3,3-trifluoropropyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3- azabicyclo[3.2.2]nonan-3-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 8-methyl-3,8- diazabicyclo[3.2.1]octan-3-yl, 3-(dimethylamino)-8-azabicyclo[3.2.1]octan-8-yl, 3-(3,3- difluorocyclobutyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(oxetan-3-yl)-3,8-diazabicyclo-[3.2. l]octan-8-yl, 5-methyl-2,5-diazabicyclo[2.2.2]octan-2-yl, 3-hydroxy-3-methyl-8- azabicyclo[3.2. l]octan-8-yl, 3-cyano-3-methyl-8-azabicyclo[3.2. l]octan-8-yl, 3-(4,4-difluoro- cyclohexyl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(tetrahydro-2H-pyran-4-yl)-3,8-diazabicyclo- [3.2.1]octan-8-yl, 8-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl, 3-(l,l-dioxidotetrahydro- 2H-thiopyran-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-benzyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-phenyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3- (tetrahydrofuran-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl, 3-(l,l-dioxidothietan-3-yl)-3,8- diazabicyclo[3.2.1]octan-8-yl, 3-(3-hydroxy-3-methylcyclobutyl)-3,8-diazabicyclo[3.2.1]octan-8- yl, 3,3-dioxido-3-thia-8-azabicyclo[3.2. l]octan-8-yl, 3-(3-cyano-3-methylcyclobutyl)-3,8- diazabicyclo[3.2.1]octan-8-yl, 3-cyclobutyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 2-(l-cyano-7- azabicyclo[2.2.1]heptan-7-yl, 4-(3,3-difluorocyclobutyl)-2,6-dimethylpiperazin-l-yl, 7-methyl-3- oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl, or 3-cyclopropyl-3,8-diazabicyclo[3.2.1]octan-8-yl.124. In embodiment 124A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, and 5 A to 74A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are independently hydrogen, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, bicyclic cycloalkyl, bicyclic heterocyclyl, spiro heterocyclyl, aryl, aralkyl, heteroaryl, or heteroaralkyl (aryl, aralkyl, heteroaryl, and heteroaralkyl are absent in Formula (IIB)), wherein bicyclic cycloalkyl of R8and R9are substituted with one or two Ra; bicyclic heterocyclyl of R8and R9are substituted with Rb, Rc, and Rdand aryl, by itself or as part of aralkyl and heteroaryl, by itself or as part of heteroaralkyl, of R8and R9are substituted with Rh, R1, and Rk.125A. In embodiment 125A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 74 A and 124 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, amino, alkylamino, dialkylamino, substituted amino, phenyl, phenylalkyl, heteroaryl, or heteroaralkyl wherein phenyl and heteroaryl, either by itself or as part of phenylalkyl and heteroaralkyl, of R9and R10are substituted with Rh, R1, and Rk.126A. In embodiment 126A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 2A, 5A to 74 A, 124 A, and 125 A, or a pharmaceutically acceptable salt thereof, wherein R8and R9are 3-hydroxy- 1,1 -dimethylethyl, 1 -hydroxy- 1 -methylethyl, difluoromethyl, 1 -fluoro- 1 -methylethyl, 1- m ethoxy- 1 -methylethyl, 1 -cyano- 1 -methylethyl, 12-cyano- 1,1 -dimethylethyl, 1 -fluoro- 1- methylethyl, phenyl, 2,6-difluorophenyl, 2,6-dichlorophenyl, 2-methylphenyl, 2-chloro-6- fluorophenyl, 2-chlorophenyl, 2-fluorophenyl, 2-methylphenyl, 2-fluoro-6-methylphenyl, pyridin- 4-yl, 1,1 -dimethyl -2-methylsulfonylethyl, 1-methyl-l-phenylethyl, 1 -methyl- 1-pyri din-3 -ylethyl, amino, methylamino, dimethylamino, diethylamino, N-methyl-N-phenylamino, N-methyl-N-(2- fluorophenyl)amino, N,N-bis cyclopropylamino, or bicyclo[3.1.0]hexyl.127A. In embodiment 127A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75A and 82A to 126A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIA) is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, or heteroaryl, wherein heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, and heteroaryl are substituted with Rx, Ry, and Rylas defined therein.128A. In embodiment 128A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 2A, 5A to 75A and 82 A to 126 A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIB) is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, spiro cyclylsulfoximinyl are substituted with Rx, Ry, and Rylas defined therein.129A. In embodiment 129A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A, 17A to 69A, and 75 A to 81 A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIC) is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl,bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, spiro cyclyl sulfoximinyl are substituted with Rx, Ry, and Rylas defined therein.130A. In embodiment 130A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 4A, and 17A to 69A, and 75 A to 81 A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIC 1) is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14,- Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, and spiro cyclylsulfoximinyl are substituted with Rx, Ry, and Rylas defined therein.131 A. In embodiment 131 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q-(alk1)ni-SO2R10, - Q1-(alk2)n2-132A. In embodiment 132A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q-(alk1)ni-SO2R10.133A. In embodiment 133A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q2-(alk3)n3-SO2NR13R14.134A. In embodiment 134A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q1-(alk2)n2-SO(=NR11)R12.135 A. In embodiment 135 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 3 A, 5Ato 129A and 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q3-(alk4)n4- COR15.136A. In embodiment 136A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q4-(alk5)n5-CONR16R17.137A. In embodiment 137A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q5-(alk6)n6'NR18COR19.138A. In embodiment 138A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein R5is -Q6-(alk7)n7-NR20SO2R21.139A. In embodiment 139A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 138A, or a pharmaceutically acceptable salt thereof, is wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.140A. In embodiment 140A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, or spiro cycloalkyl, where each of the aforementioned rings is substituted with Rvand Rw.141A. In embodiment 141A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 140A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl substituted with Rvand Rw.142A. In embodiment 142A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is bridged cycloalkyl substituted with Rvand Rw.143A. In embodiment 143A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 140A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is spiro cycloalkyl substituted with Rvand Rw.144A. In embodiment 144A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, or spiro heterocyclylA, where each of the aforementioned rings is substituted with Rvand Rw.145A. In embodiment 145A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A and 144A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is heterocyclylAor bicyclic heterocyclylA, where each of the aforementioned rings is substituted with Rvand Rw.146A. In embodiment 146A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, 144A, and 145A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is heterocyclylAsubstituted with Rvand Rw.147A. In embodiment 147A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, 144A, and 145A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is bicyclic heterocyclylAsubstituted with Rvand Rw.148A. In embodiment 148A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, and 144A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5,and Q6is bridged heterocyclylAor spiro heterocyclylA, where each of the aforementioned rings is substituted with Rvand Rw.149A. In embodiment 149A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, 144A, and 148A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is spiro heterocyclylAsubstituted with Rvand Rw.150A. In embodiment 150A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is aryl or heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.151A. In embodiment 151A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A and 150A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is phenyl or 6 -membered heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.152A. In embodiment 152A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 139A, 150A, and 151 A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is phenyl substituted with Rvand Rw.153 A. In embodiment 153 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 152A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is other than bond and each of n1, n2, n3, n4, n5, n6, and n7is 0.154A. In embodiment 154A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 152A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is other than bond and each of n1, n2, n3, n4, n5, n6, and n7is 1.155A. In embodiment 155A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 152A and 154A, or a pharmaceutically acceptable salt thereof, wherein each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is methylene or ethylene.156A. In embodiment 156A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 152A, 154A, and 155 A, or a pharmaceutically acceptable salt thereof, wherein each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is methylene.157A. In embodiment 157A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 152A and 154A, or a pharmaceutically acceptable salt thereof, wherein each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is ethylene, propylene, butylene, or pentylene.158A. In embodiment 158A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 152A, 154A, and 157A, or a pharmaceutically acceptable salt thereof, wherein each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is ethylene or butylene.159A. In embodiment 159A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75 A, 82 A to 127 A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIA) is heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein each ring is substituted with Rx, Ry, and Rylas defined therein.160A. In embodiment 160A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 2A, 5A to 75A, 82A tol26A and 128A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIB) is cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein each ring is substituted with Rx, Ry, and Rylas defined therein.161A. In embodiment 161A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 3 A and 17A to 69A, 75 A to 81 A, and A129A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIC) is cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein each ring is substituted with Rx, Ry, and Rylas defined therein.162A. In embodiment 162A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 4A and 17A to 69 A, 75 A to 81 A, and A130A, or a pharmaceutically acceptable salt thereof, wherein R5for compounds of Formula (IIC 1) is cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein each ring is substituted with Rx, Ry, and Rylas defined therein.163 A. In embodiment 163 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75 A, 82A to 127A, and 159A, or a pharmaceutically acceptable salt thereof, wherein R5is heterocyclyl substituted with Rx, Ry, and Rylas defined therein.164A. In embodiment 164A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75 A, 82A to 127A and 159A, or a pharmaceutically acceptable salt thereof, wherein R5is bicyclic heterocyclyl substituted with Rx, Ry, and Rylas defined therein.165 A. In embodiment 163 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 2A, to 126A, 128A to 130A, and 160A to 162A, or a pharmaceutically acceptable salt thereof, wherein R5is cyclylsulfonyl, each ring substituted with Rx, Ry, and Rylas defined therein.166A. In embodiment 166A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 2A to 126A, 128A to 130A, and 160A to 162A , or a pharmaceutically acceptable salt thereof, wherein R5is bicyclylsulfonyl, each ring substituted with Rx, Ry, and Rylas defined therein.167A. In embodiment 167A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 162A, or a pharmaceutically acceptable salt thereof, wherein R5is spiro heterocyclyl substituted with Rx, Ry, and Rylas defined therein.168 A. In embodiment 166A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 162A, or a pharmaceutically acceptable salt thereof, wherein R5is cyclylsulfoximinyl or bicyclylsulfoximinyl, each ring substituted with Rx, Ry, and Rylas defined therein.169A. In embodiment 169A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 162A, or a pharmaceutically acceptable salt thereof, wherein R5is spiro sulfoximinyl substituted with Rx, Ry, and Rylas defined therein.170A. In embodiment 170A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75A, and 82A to 127A, or a pharmaceutically acceptable salt thereof, wherein R5is aryl or heteroaryl, wherein each of the aforementioned ring is substituted with Rx, Ry, and Rylas defined therein.171A. In embodiment 171A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75 A, 82A to 127A, and 170A, or a pharmaceutically acceptable salt thereof, wherein R5is phenyl substituted with Rx, Ry, and Rylas defined therein.172A. In embodiment 172A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75 A, 82A to 127A, and 170A, or a pharmaceutically acceptable salt thereof, wherein R5is 6- membered heteroaryl substituted with Rx, Ry, and Rylas defined therein.173 A. In embodiment 173 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 172A, or a pharmaceutically acceptable salt thereof, wherein R5is where:(1) the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are where the: cycloalkyl is: bridged cycloalkyl isrespectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and (2) the heterocyclyl, bridged heterocyclyl, bicyclic heterocyclyl, cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, spiro sulfoximinyl, bicyclylsulfoximinyl, cyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where: heterocyclyl is:also referred to as cyclylsulfonylbridged heterocyclyl is:also referred to as bicyclylsulfonylspiro heterocyclyl is:cycl lsulfoximin l is:bicyclyl sulfoximinyl is:fused heteroaryl is:respectively, wherein each ring in (2) is substituted as defined therein; and * wherein in each ring in (1) and (2) above, denotes bond to NH of -NHR5moiety in the compound of Formula (I); andin each ring in (1) denotes bond to remainder of -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15, -Q4-(alk5)n5- CONR16R17, -Q5-(alk6)n6NR18COR19, or -Q6-(alk6)n7-NR20SO2R21.174A. In embodiment 174A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173 A, or a pharmaceutically acceptable salt thereof, is wherein R5is where:(1) the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are where the:respectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and(2) the heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, bicyclic heterocyclyl, cyclylsulfonyl, bicyclylsulfonyl, spiro sulfoximinyl, bicyclylsulfoximinyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:heterocyclyl is:bicyclic heterocyclyl is:bicyclylsulfonyl spiro sulfoximinyl is:cyclylsulfoximinyl is:aryl is: heteroaryl is:fused heteroaryl is:respectively, wherein each ring in (2) is substituted as defined therein; and \ whereineach ring in (1) and (2) and in each ring in (1) have the same meaning as in embodiment 173 A.175A. In embodiment 175A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, or a pharmaceutically acceptable salt thereof, wherein R5is where:(1) the cycloalkyl, bridged cycloalkyl, heterocyclylA, bicyclic heterocyclylA, spiro heterocyclylA, and arespectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and(2) the heterocyclyl, bicyclic heterocyclyl, bicyclylsulfonyl spiro heterocyclyl, spiro sulfoximinyl, bicyclylsulfoximinyl, aryl, and heteroaryl of R5are where: heterocyclyl is: bicyclic heterocyclic is: spiro heterocyclyl is:bicyclylsulfonyl spirosrespectively, wherein each ring in (2) is substituted as defined therein; and whereineach ring in (1) and (2); and in each ring in (1) have the same meaning as in embodiment 173A andin each ring in (2) denotes attachment to one of Rx, Ry, and Ryl.176A. In embodiment 176A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173 A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are:\ *1respectively, wherein each ring is substituted as defined therein and wherein andxin each ring have the same meaning as in embodiment 173 A.177A. In embodiment 177A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173 A, 174A, and 176A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are:respectively, where each ring is substituted as defined therein; and wherein and ^ Mn each ring have the same meaning as in embodiment 173 A.178 A. In embodiment 178 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173 A, 174A, 176A, and 177A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl, bridged cycloalkyl, heterocyclylA, bicyclic heterocyclylA, spiro heterocyclylA, and aryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are:respectively, where each ring is substituted as defined therein; and whereineach ring have the same meaning as in embodiment 173 A.179A. In embodiment 179A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, 176A, and!77A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and bridgedcycloalkyl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:respectively, and each ring is substituted as defined therein; and wherein and 'in each ring have the same meaning as in embodiment 173 A.180A. In embodiment 180A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, 176A, 177A, and 179A, or a pharmaceutically acceptable salt thereof, wherein the heterocyclylAof each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is: 6. and is substituted as defined therein; and wherein and ^ 'in each ring have the same meaning as in embodiment 173 A.181A. In embodiment 181A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, 176A, 179A, and 180A, or a pharmaceutically acceptable salt thereof, wherein the spiroheterocyclylAof each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:and is substituted as defined therein; and wherein and ^ 'in each ring have the same meaning as in embodiment 173 A.182A. In embodiment 182A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 175A, 176A, and 179A to 181A, or a pharmaceutically acceptable salt thereof, wherein the bicyclyl heterocyclylAof each Q, Q1, Q2, Q3, Q4, Q5, and Q6is:each ring is substituted as defined therein; and wherein and ^ Mn each ring have the same meaning as in embodiment 173 A.183 A. In embodiment 183 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, 176A, 177A, and 179A to 182A, or a pharmaceutically acceptable salt thereof, wherein the aryl of ; each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is: —J— and is substituted as defined therein; and wherein and have the same meaning as in embodiment 173 A.184A. In embodiment 184A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, 176A, and 179A to 183 A, or a pharmaceutically acceptable salt thereof, wherein the bridged cycloalkyl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:and is substituted as defined therein; and whereinhave the same meaning as in embodiment 173.185 A. In embodiment 185 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 174A, 176A, and 179A to 183 A, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is:and is substituted as defined therein; and whereinhave the same meaning as in embodiment 173.186A. In embodiment 186A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173Aand 176A to 185 A, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl, bicyclic heterocyclyl, cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicycyclyl sulfoxaminyl, spiro sulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:bicyclylsulfonyl bicyclyl sulfoximinyl is:heteroa fused heteroaryl is:ryl is:respectively, wherein each ring is substituted as defined therein; and\ * wherein in each ring has the same meaning as in embodiment 173 A.187A. In embodiment 187A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173A and 176A to 186A, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl, bicyclic heterocyclyl, cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, spiro sulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:l is:respectively, and each ring is substituted as defined therein; and\ * wherein in each ring have the same meaning as in embodiment 178 A.188 A. In embodiment 188 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 173A and 176A to 187A, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl, bicyclic heterocyclyl, bicyclylsulfonyl, spiro heterocyclyl, spiro sulfoximinyl, aryl, and heteroaryl, of R5are where: clyl is:spirosulfoximinyl is: aryl is: heteroaryl is:respectively, where each ring is substituted as defined therein; and wherein and ^ 'in each ring have the same meaning as in embodiment 174 A.189A. In embodiment 189A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or apharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 127A, 159A, 163 A, 173 A, 174A, and 176A to 188A, or a pharmaceutically acceptable salt heterocyclyl is:thereof, wherein the heterocyclyl of R5is:and is substituted as defined therein and\ * \ wherein and have the same meaning as in embodiment 175 A.190A. In embodiment 190A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A, 160A to 162A, 167A, 173 A, 174A, 176A to 187A, and 189A, or a pharmaceutically acceptable salt thereof, wherein the spiro heterocyclyl,and is substituted as defined therein; and\ * wherein has the same meaning as in embodiment 173 A.191A. In embodiment 191A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to 75A, 82A to 127A, 159A, 164A, and 173A to 190A, or a pharmaceutically acceptable salt thereof, is wherein the bicyclic heterocyclyl, of R5is:each ring is substituted as defined therein; ; and whereinin each ring have the same meaning as in embodiment 175 A.192A. In embodiment 192A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A, 5A to75A, 82A to 127A, 170A, 173 A, to 191 A, or a pharmaceutically acceptable salt thereof, wherein the aryl of R5is;is substituted as defined therein; and wherein and '' have the same meaning as in embodiment 175 A.193 A. In embodiment 193, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A, 159A to 162A, 164A, 166A, 173 A, 174A, and 176A to 192A , or a pharmaceutically acceptable salt thereof, wherein the bicyclic heterocyclyl and bicyclylsulfonyl of R5areand each ring is substituted with Rx, Ry, and Ryl; and\ * wherein in each ring has the same meaning as in embodiment 173.194A. In embodiment 194A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 3 A, 5A to 138A, or a pharmaceutically acceptable salt thereof, wherein each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond.195 A. In embodiment 195 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 138A and 194, or a pharmaceutically acceptable salt thereof, wherein each of alk2, alk3, alk4, alk5, alk6, and alk7is ethylene, propylene, butylene, or pentylene and each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond.196A. In embodiment 196A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 183 A, 194 A, and 195 A, or a pharmaceutically acceptable salt thereof, wherein each of alk2, alk3, alk4, alk5, alk6, and alk7is ethylene or butylene and each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond.197A. In embodiment 197A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, 134A, 137A to 158A, and 173A to 196A, or a pharmaceutically acceptable salt thereof, wherein R11, R18, and R20are hydrogen or alkyl (such as methyl, ethyl, or propyl).198 A. In embodiment 198 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, 134A, 137A to 158A, and 173A to 197A, or a pharmaceutically acceptable salt thereof, wherein R11, R18, and R20are hydrogen.199A. In embodiment 199A, the compound of Formulae (IIA), (IIB), (IIC), (IIC1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 131 A, 134A, 137A to 158A, and 173A to 197A, or a pharmaceutically acceptable salt thereof, wherein R11, R18, and R20are methyl, ethyl, or propyl.200A. In embodiment 200A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 158A, and 173 to 199A, or a pharmaceutically acceptable salt thereof, wherein:R15and R19are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, and heterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R10and R21are independently selected from alkyl, cycloalkyl, haloalkyl, fluoro, chloro, - CR22=CR23R24, aryl, aralkyl, heteroaryl, heteroaralkyl, and heterocyclyl wherein cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and heterocyclyl which is substituted with one to three substituentsindependently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.200A1. In embodiment 200A1, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 158A, and 173 to 200A, or a pharmaceutically acceptable salt thereof, wherein:R10, R15, R19, and R21are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, and heterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and heterocyclyl which is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.200A2. In embodiment 200A2, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 158A, and 173 to 200A, or a pharmaceutically acceptable salt thereof, wherein:R15and R19are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, andheterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R10and R21are independently selected from alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein cycloalkyl, aryl, heteroaryl, and heterocyclyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and heterocyclyl which is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.201 A. In embodiment 201 A, the compound or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 158A and 173 to 200A2, or a pharmaceutically acceptable salt thereof, wherein:R10, R15, R19, and R21are methyl, ethyl, vinyl, fluoro, 2-dimethylaminovinyl, 2- di ethylaminovinyl, 2-diisopropylaminovinyl, l-cyano-2-dimethylaminovinyl, 2- ethylisopropylaminovinyl, l-cyano-2,2-dimethylpropen-l-yl, piperazinyl, 4-methylpiperazinyl, 4- ethylpiperzin-l-yl, 2-m ethoxy ethylpiperazinyl, or morpholin-4-yl;R12is methyl, ethyl, propyl, or vinyl;R13, R14, R16, and R17are independently hydrogen, methyl, ethyl, aminoethyl, methylaminoethyl, dimethylaminoethyl, 2-hydroxy ethyl, di ethylaminoethyl, azeti din-3 -yl, 1- m ethylazeti din-3 -yl, l-ethylazetidin-2-yl, l-methylpyrrolidin-3-yl, l-ethylpyrrolidin-3-yl, 1- methylpiperidinyl, or 1-ethylpiperidinyl.202A. In embodiment 202A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 158A and 173A to 201 A, or a pharmaceutically acceptable salt thereof, wherein the R10is methyl.203 A. In embodiment 203 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 202A, or a pharmaceutically acceptable salt thereof, wherein Rx, Ry, and Rylwhere Rxand Ryare independently selected from hydrogen, deuterium, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, and cyano and Rylis hydrogen, deuterium, alkyl, alkoxy, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl or aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl).204A. In embodiment 204A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 203 A, or a pharmaceutically acceptable salt thereof, wherein Rxand Ryare independently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, and cyano and Rylis hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, aminocarbonyl, aminocarbonylalkyl, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl or aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl).205 A. In embodiment 205 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 204A, or a pharmaceutically acceptable salt thereof, wherein Rxand Ryare independently selected from hydrogen, deuterium, and alkyl and Rylis hydrogen heterocyclyl, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy (wherein heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, or heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl).206A. In embodiment 206A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A and 159A to 204A, or a pharmaceutically acceptable salt thereof, wherein Rxand Ryare independently selected from hydrogen and methyl and Rylis hydrogen, deuterium, acyl, aminocarbonyl, aminocarbonylalkyl, aminoalkyl, or heterocyclyl, wherein heterocyclyl is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy carbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, and heterocyclyl. In one embodiment of embodiment 185, Rxand Ryare independently selected from hydrogen and methyl and Rylis hydrogen.207A. In embodiment 207A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 206A, or a pharmaceutically acceptable salt thereof, wherein R5is 3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, 4-(methylsulfonyl)cyclohexyl, 2,2-dioxidohexahydro-lH- cy cl openta[c]thi ophen-5 -yl, l-(methylsulfonyl)piperidin-4-yl, l-(methylaminosulfonyl)-piperidin- 4-yl, l-(aminosulfonyl)piperidin-4-yl, 4-(piperazin-l-yl)phenyl, 4-methylsulfonylphenyl, 4- dimethylaminom ethylphenyl, 4-(4-methylpiperazin-l-yl)phenyl, 4-(vinylsulfonyl)phenyl, 4- aminosulfonylphenyl, 4-((2-(dimethylamino)vinyl)-sulfonyl)phenyl, l-acetylpiperidin-4-yl, 1- fluorosulfonylpiperidin-4-yl, l-acryloylpiperidin-4-yl, 4-(3-(dimethylamino)acryloyl)phenyl, 4- (vinylsulfonimidoyl)phenyl, l-(3-(diethylamino)-acryloyl)piperidin-4-yl, l-(3- (diisopropylamino)acryloyl)piperidin-4-yl, l-(2-cyano-3-(dimethylamino)acryloyl)piperidin-4-yl, 4-(2-(diethylamino)vinyl)sulfonylphenyl, 4-((2-(diethylamino)vinyl)sulfonyl)phenyl, 4-((2- (ethyl(isopropyl)amino)vinyl)sulfonyl)phenyl, l-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-4- yl, 4-(2-(diisopropylamino)vinyl)sulfonylphenyl, 4-((l-cyano-2- (dimethylamino)vinyl)sulfonyl)phenyl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, 1- (methylsulfonyl)azepan-4-yl, 2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl, 3- (methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3- azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 5- (piperazin- 1 -yl)pyridin-2-yl, 1 -aminosulfonylpiperidin-4-yl, 1 -methylaminosulfonylpiperidin-4-yl, 1 -(4-(2-m ethoxy ethyl)piperazin- 1 -yl)piperidin-4-yl, 1 -dimethylamino-sulfonylpiperidin-4-yl, 4- piperazin- 1 -ylphenyl, 1 -piperazin- 1 -ylsulfonylpiperidin-4-yl, 1 -(N-(2-dimethylaminoethyl)-N- methylaminosulfonyl)piperidin-4-yl, l-(N,N-bis-(hydroxyethyl)aminosulfonyl)piperidin-4-yl, 1- (4-methylpiperazin-l-ylsulfonyl)piperidin-4-yl, l-((2-dimethylaminoethylamino)sulfonyl)- piperidin-4-yl, 2-methylsulfonylethyl, 4-(S-methylsulfonimidoyl)cyclohexyl, 1- (methylsulfonyl)piperidin-3-yl, l-(methylsulfonyl)-4,5,6,7-tetrahydro-lH-indazol-5-yl, 3- (methylsulfonyl)propyl, 4-(piperazin-l-ylsulfonyl)cyclohexyl, 1 -(N-(l-m ethylazeti din-3 -yl)-N- methylaminosulfonyl)piperidin-4-yl, 1, l-dioxidotetrahydro-2H-thiopyran-4-yl, 2- aminosulfonylethyl, 1 -imino- l-oxidohexahydro-116-thiopyran-4-yl, 2,2-dioxido-2- thiaspiro[3.3]heptan-6-yl, 1 -(methylimino)- l-oxidohexahydro-116-thiopyran-4-yl, l-(N-(azetidin- 3-yl)-N-methylaminosulfonyl)piperidin-4-yl, 2-imino-2-oxido-216-thiaspiro[3.3]heptan-6-yl, (lR,5S,6s)-3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, (lR,5S,6r)-3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, (4aR,6S)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (3 aR, 5 s,6aS)-2,2-dioxidohexahydro-lH-cyclopenta[c]thiophen-5-yl, l-(methylsulfonylmethyl)piperidin-4-yl, 7,7- dioxido-7-thiaspiro[3.5]nonan-2-yl, 4-(4-(2-methoxyethyl)piperazin-l-yl)phenyl, 4-(l- methylpiperazin- 1 -yl)phenyl, 5-(piperazin- 1 -yl)pyridin-2-yl, 1 , 1 -di oxidotetrahydrothi ophen-3 -yl, 2-fluoro-4-methylsulfonylphenyl, 2-methyl-4-methylsulfonylphenyl, ((lr,3r)-3- (methylsulfonyl)cyclobutyl, 3-((methylsulfonyl)methyl)-bicyclo[l .1. l]pentan-l-yl, 3-(N- methylmethylsulfonamido)bicyclo-[l .1. l]pentan-l-yl, 3-((dimethylaminocarbonyl)- methyl)bicyclo[l .1. l]pentan-l-yl, (lr,3r)-3-(N-methylmethyl-sulfonamido)cyclobutyl, 3- ((methylsulfonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, 3-((N,N-dimethylsulfamoyl)methyl)- bicyclo[l. l.l]pentan-l-yl, 2-(methylimino)-2-oxido-216-thiaspiro[3.3]heptan-6-yl, 3- (sulfamoylmethyl)bicyclo[l .1. l]pentan-l-yl, 3-((S-methylsulfonimidoyl)methyl)- bicyclof 1.1.1 ]pentan- 1 -yl, 1 -aminosulfonylpiperidin-4-yl, 3 -(2-(4-methylpiperazin- 1 -yl)-2- oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 -yl, 3 -(2-(4-,morpholin-4-yl)-2-oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 - yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)-3-fluoro-l- (methylsulfonyl)piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4-yl.208 A. In embodiment 208 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 207A, or a pharmaceutically acceptable salt thereof, wherein R5is 3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, 4-(methylsulfonyl)cyclohexyl, 2,2-dioxidohexahydro-lH- cy cl openta[c]thi ophen-5 -yl, l-(methylsulfonyl)piperidin-4-yl, l-(methylaminosulfonyl)piperidin- 4-yl, l-(aminosulfonyl)piperidin-4-yl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 1- acetylpiperidin-4-yl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, l-(methylsulfonyl)azepan-4- yl, 2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl, 3 -(methyl sulfonyl)-3- azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2- (((lR,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, l-aminosulfonylpiperidin-4-yl, 1- methylaminosulfonylpiperidin-4-yl, 1 -dimethylamino-sulfonylpiperidin-4-yl 1 -piperazin- 1 - ylsulfonylpiperidin-4-yl, l-(N-(2-dimethylaminoethyl)-N-methylaminosulfonyl)piperidin-4-yl, 1- (N,N-bis-(hydroxyethyl)aminosulfonyl)piperidin-4-yl, l-(4-methylpiperazin-l- ylsulfonyl)piperidin-4-yl, l-((2-dimethylaminoethylamino)sulfonyl)-piperidin-4-yl, 2- methylsulfonylethyl, 4-(S-methylsulfonimidoyl)cyclohexyl, l-(methylsulfonyl)piperidin-3-yl, 3- (methylsulfonyl)propyl, l-(N-(l-methylazeti din-3 -yl)-N-methylaminosulfonyl)piperidin-4-yl, 1,1- dioxidotetrahydro-2H-thiopyran-4-yl, 2-aminosulfonylethyl, 1 -imino- 1-oxidohexahydro- 116- thiopyran-4-yl, 2,2-dioxido-2-thiaspiro[3.3]heptan-6-yl, 1 -(methylimino)- 1-oxidohexahydro- 116- thiopyran-4-yl, l-(N-(azeti din-3 -yl)-N-methylaminosulfonyl)piperidin-4-yl, 2-imino-2-oxido-216-thiaspiro[3.3]heptan-6-yl, (lR,5S,6s)-3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, (lR,5S,6r)-3,3- dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, (4aR,6S)-l,l-dioxidooctahydropyrido[l,2- b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b ] [ 1 ,2,6]thiadiazin-6-yl, (3aR,5s,6aS)-2,2-dioxidohexahydro-lH-cyclopenta[c]thiophen-5-yl, 1- (methylsulfonylmethyl)piperidin-4-yl, 7,7-dioxido-7-thiaspiro[3.5]nonan-2-yl, 1,1- di oxidotetrahydrothi ophen-3 -yl, 2-fluoro-4-methylsulfonylphenyl, 2-methyl-4- methylsulfonylphenyl, ((lr,3r)-3-(methylsulfonyl)cyclobutyl, 3 -((methyl sulfonyl)methyl)- bicyclof 1.1.1 ]pentan- 1 -yl, 3 -(N-methylmethylsulfonamido)bicyclo[ 1.1.1 ]pentan- 1 -y 1 , 3 - ((dimethylaminocarbonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, (lr,3r)-3-(N- methylmethylsulfonamido)cyclobutyl, 3-((methylsulfonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, 3- ((N,N-dimethylsulfamoyl)methyl)-bicyclo[l .1. l]pentan-l-yl, 2-(methylimino)-2-oxido-216- thiaspiro[3.3 ]heptan-6-yl, 3 -(sulfamoylmethyl)bicyclo[ 1.1.1 ]pentan- 1 -yl, 3 -((S- methylsulfonimidoyl)methyl)-bicyclo[l .1. l]pentan-l-yl, l-aminosulfonylpiperidin-4-yl, 3-(2-(4- methylpiperazin-l-yl)-2-oxoethyl)bicyclo[l .1. l]-pentan-l-yl, 3-(2-(4-morpholin-4-yl)-2- oxoethyl)bicyclo[l .1. l]-pentan-l-yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)-3-fluoro-l-(methylsulfonyl)-piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4- yi.209A. In embodiment 209A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 208A, or a pharmaceutically acceptable salt thereof, wherein R5is l-(methylsulfonyl)piperidin-4-yl, 1- (methylaminosulfonyl)piperidin-4-yl, l-(aminosulfonyl)piperidin-4-yl, 4-methylsulfonylphenyl,4-aminosulfonylphenyl, l-acetylpiperidin-4-yl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, 1- (methylsulfonyl)azepan-4-yl, 2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl, 3- (methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3- azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 1- aminosulfonylpiperidin-4-yl, 1 -methylaminosulfonylpiperidin-4-yl, 1 -dimethylamino- sulfonylpiperidin-4-yl l-piperazin-l-ylsulfonylpiperidin-4-yl, l-(N-(2-dimethylaminoethyl)-N- methylaminosulfonyl)piperidin-4-yl, 1 -(N,N-bis-(hydroxyethyl)aminosulfonyl)piperidin-4-yl, 1 - (4-methylpiperazin-l-ylsulfonyl)-piperidin-4-yl, l-((2-dimethylaminoethylamino)sulfonyl)- piperidin-4-yl, 2-methylsulfonylethyl, 4-(S-methylsulfonimidoyl)cyclohexyl, 1- (methylsulfonyl)piperidin-3-yl, 3-(methylsulfonyl)-propyl, l-(N-(l-methylazetidin-3-yl)-N- methylaminosulfonyl)piperidin-4-yl, 1 , 1 -dioxidotetrahydro-2H-thiopyran-4-yl, 2- aminosulfonylethyl, 1 -imino- l-oxidohexahydro-116-thiopyran-4-yl, 1 -(methylimino)- 1-oxidohexahydro-116-thiopyran-4-yl, l-(N-(azeti din-3 -yl)-N-methylaminosulfonyl)piperidin-4-yl,2-imino-2-oxido-216-thiaspiro[3.3]heptan-6-yl, (4aR,6S)-l,l-dioxidooctahydropyrido[l,2- b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidoocta-hydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, 1 - (methylsulfonylmethyl)piperidin-4-yl, 7,7-dioxido-7-thiaspiro[3.5]nonan-2-yl, 1,1- di oxidotetrahydrothi ophen-3 -yl, 2-fluoro-4-methylsulfonylphenyl, 2-methyl-4- methylsulfonylphenyl, ((lr,3r)-3-(methylsulfonyl)cyclobutyl, 3 -((methyl sulfonyl)- methyl)bicyclo[l .1. l]pentan-l-yl, 3-(N-methylmethylsulfonamido)-bicyclo[l .1. l]pentan-l-yl, 3- ((dimethylaminocarbonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, (lr,3r)-3-(N-methylmethyl- sulfonamido)cyclobutyl, 3-((methylsulfonyl)-methyl)bicyclo[l .1. l]pentan-l-yl, 3-((N,N- dimethylsulfamoyl)methyl)bicyclo[l .1. l]pentan-l-yl, 2-(methylimino)-2-oxido-216- thiaspiro[3.3]heptan-6-yl, 3-(sulfamoylmethyl)bicyclo[l.l. l]pentan-l-yl, 3-((S- methylsulfonimidoyl)methyl)bicyclo[l .1. l]pentan-l-yl, l-aminosulfonylpiperidin-4-yl, 3-(2-(4- methylpiperazin-l-yl)-2-oxoethyl)bicyclo[l .1. l]-pentan-l-yl, 3-(2-(4-morpholin-4-yl)-2- oxoethyl)bicyclo[l .1. l]-pentan-l-yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4- yi.210A. In embodiment 210A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 132A, 139A, 144A to 146A, 153A, 159A to 162A, 164A, 166A, 169A, 173A to 178A, 180A, 186A to 188 A, 190A, 193 A, and 200A to 209A, or a pharmaceutically acceptable salt thereof, wherein R5is l-methylsulfonylpiperidin-4-yl, 2-methyl-l-methylsulfonylpiperidin-4-yl, 2,2-dioxido-2- thiaspiro[3.3]heptan-6-yl, 3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, 2,2-dioxidohexahydro-lH- cyclopenta[c]thiophen-5-yl, or 2-imino-2-oxido-216-thiaspiro[3.3]heptan-6-yl.211 A. In embodiment 211 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 132A, 139A to 141 A, 153A, 159A to 162A, 167A, 173A to 179A, 185A to 188A, 190A, and 200 to 206A or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula (i) or (ii):(i) (ii)where alk is alkyl and each ring is substituted with Rvand Rw.212A. In embodiment 212A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 132A, 139A to 141 A, 153A, 173A to 179A, 185A, and 200A to 202A and 211 A, or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula (i):<i) where alk is alkyl and the ring of formula (i) is substituted with Rvand Rw.213 A. In embodiment 213 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 132A, 139A to 141 A, 153A, 173A to l79A, 185 A, and 200 A to 202 A, 211 A, and 212 A, or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula (i):where alk is alkyl, Rvis hydrogen, and Rwis fluoro or methyl which is attached at carbon that is meta to the carbon substituted with -SChalk.214A. In embodiment 192, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 132A, 139A to 141 A, 153A, 173A to 179A, 185A, and 200A to 202A, 211 A, and 212A , or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula (i):where alk is alkyl and Rvand Rware hydrogen.215 A. In embodiment 215 A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 132A, 139A to 141 A, 153A, 173A to l79A, 185 A, and 200 A to 202 A, 211 A, 212A, and 214 A, or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula:216A. In embodiment 216A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A, 153A, 159A to 162A, 167A, 173A to l75A, 186A to l88A, 190A, and 203A to 211A , or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula (ii):where the ring of formula (ii) is substituted as defined therein.217A. In embodiment 217A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la), (lb), (Ic), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A, 153A, 159A to 162A, 167A, 173A to 175A, 186A to 188A, 190A, and 203 A to 211 A, or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula:218 A. In embodiment 218A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any one of embodiments 1 A to 130A, 153A, 159A to 162A, 164A, 173A to 175A, 186A to 188A, 193 A, and 203A to 210A , or a pharmaceutically acceptable salt thereof, wherein R5is a ring of formula (iii) or (iv):(iii) (iv) where each ring is substituted as defined therein.219A. In embodiment 219A, the compound of Formulae (IIA), (IIB), (IIC), (IIC 1 ), (la),(lb), (Ic), (Id), (le), (If), (Ig), (Ih), (li), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq), or a pharmaceutically acceptable salt thereof, is as provided in any...

Claims

CLAIMSWhat is Claimed:

1. A method of treating cancer by inhibition of CDK2 comprising administering to the patient in need thereof a compound of Formula (I):wherein:W is N, CH, or C when attached to R4;R8is hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, wherein:(A) cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8are substituted with one or two Raindependently selected from hydrogen, deuterium, alkyl, deuteroalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, alkylamino, and dialkylamino;(B) heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8are substituted with Rb, Rc, and Rdindependently selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl (wherein cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl are substituted with one or two substituents independently selected from hydrogen, alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, hydroxy, cyano, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, heteroaryl, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl are substituted with Re, Rf, and Rgindependently selected from hydrogen,alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, amino, alkylamino, and dialkylamino); and(C) aryl, by itself or as part of aralkyl, and heteroaryl, by itself or as part of heteroaralkyl, of R8are substituted with Rh, R1, and Rkindependently selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl (wherein cycloalkyl is optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, hydroxy, cyano, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, heteroaryl, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl are substituted with Rm, Rn, and R° independently selected from hydrogen, alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, amino, alkylamino, and dialkylamino); ring RDis phenyl or heteroaryl;R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or cyano;Ar1is cycloalkyl, cycloalkylalkyl, fused cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, bicyclic heterocyclyl, bicyclic heterocyclylalkyl, bridged heterocyclyl, bridged heterocyclylalkyl, fused heterocyclyl, fused heterocyclylalkyl, spiro heterocyclyl, and spiro heterocyclylalkyl (wherein cycloalkyl, by itself or as part of cycloalkylalkyl, fused cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, by itself or as part of bicyclic heterocyclylalkyl, bridged heterocyclyl, by itself or as part of bridged heterocyclylalkyl, fused heterocyclyl, by itself or as part of fused heterocyclylalkyl, and spiro heterocyclyl, by itself or as part of spiro heterocyclylalkyl, are substituted with Rp, Rq, and Rrindependently selected from hydrogen, alkyl, alkoxy, alkylsulfonyl, alkyloxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl,haloalkoxy, and cyano)); provided that the heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, and spiro heterocyclyl substituted with Rp, Rq, and Rrof Ar1are attached to the -SO2- of -NHSO2- via a carbon ring atom;R4is hydrogen, alkyl, cycloalkyl, cyano, amino, halo, or haloalkyl;R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, heterocyclyl, bicyclic heterocyclyl, fused heterocyclyl, fused heteroaryl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, heteroaryl, or fused heteroaryl wherein: each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, wherein each of the aforementioned ring is substituted with Rvand Rwindependently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, and cyano; each of n1, n2, n3, n4, n5, n6, and n7is 0 or 1, provided that, when Q is a bond, then each of n1, n2, n3, n4, n5, n6, and n7is 1; each alk1, alk2, alk3, alk4, alk5, alk6, and alk7is alkylene;R11, R18, and R20are hydrogen or alkyl;R10, R12, R15, R19, and R21are independently selected from hydrogen, alkyl, fluoro, chloro, bromo, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, spiro heterocyclyl, heterocyclylalkyl, and -CR22=CR23R24[where R22is hydrogen, alkyl, or cyano, R23is hydrogen or alkyl, and R24is hydrogen, alkyl, halo, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, alkylamino, dialkylamino, -(alkylene)-NR25R26(where R25and R26are independently hydrogen, or alkyl), or heterocyclylalkyl], wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, and spiro heterocyclyl of R10, R12, R15, R19, and R21and heterocyclyl of heterocyclylalkyl of R24are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl; provided R10, R15, R29, and R21are not hydrogen;R13, R14, R16, and R17are independently selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl, wherein cycloalkyl, by itself or as part ofcycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl, by itself or as part heterocyclylalkyl, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano; and the heterocyclyl, bicyclic heterocyclyl, fused heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro cyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryloxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the compound of Formula (I) has a structure according to Formula (le):(le).

3. The method of claim 1 or 2, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, or cyano.

4. The method of any one of claims 1 to 3, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R1, R2, and R3are independently hydrogen, deuterium, methyl, ethyl, propyl, fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, methoxy, ethoxy, hydroxy, hydroxymethyl, methoxymethyl, cyano, or -CH2NH2.

5. The method of any one of claims 1 to 4, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R1is fluoro and R2and R3are hydrogen.

6. The method of any one of claims 1 to 5, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Ar1is a group of formula (al), (a2),7. The method of any one of claims 1 to 6, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Ar1is heteroaryl substituted with Rp, Rq, and Rr.

8. The method of any one of claims 1 to 7, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Rpis hydrogen, halo, haloalkyl, or haloalkoxy.

9. The method of any one of claims 1 to 8, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Rqis hydrogen, alkyl, cycloalkyl, halo, haloalkyl, haloalkoxy, alkoxy, amino, alkylamino, dialkylamino, phenoxy (where phenyl is substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano), aminoalkylamino, or aminoalkoxy.

10. The method of any one of claims 1 to 9, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Rris hydrogen, halo, alkyl, alkoxy, cyano, amino, alkylamino, dialkylamino, cycloalkyl, phenoxy, aminoalkyl, heterocyclyl (substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano), or aminoalkylamino.

11. The method of any one of claims 1 to 10, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where W is N.

12. The method of any one of claims 1 to 11, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R8is alkyl, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl, wherein:(A) cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8is substituted with one or two Ra; and(B) heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8is substituted with Rb, Rc, and Rd.

13. The method of any one of claims 1 to 12, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R8is alkyl.

14. The method of any one of claims 1 to 13, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where the alkyl of R8is methyl, ethyl, propyl, or butyl.

15. The method of any one of claims 1 to 12, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R8is cycloalkyl, bridged cycloalkyl, or spiro cycloalkyl wherein the cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8is substituted with one or two Ra.

16. The method of any one of claims 1 to 12 and 15, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl and bridged cycloalkyl of R8is selected from:wherein each cycloalkyl and bridged cycloalkyl is substituted with Raas defined therein; and each heterocyclyl and bridged heterocyclyl is substituted with Rb, Rc, and Rd.

17. The method of any one of claims 1 to 12 and 15 or 16, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where the cycloalkyl and bridged cycloalkyl of R8is selected from:wherein each cycloalkyl and bridged cycloalkyl is substituted with Raas defined therein; and heterocyclyl and bridged heterocyclyl is substituted with Rb, Rc, and Rd.

18. The method of any one of claims 1 to 12, and 15 to 17, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Rais hydrogen, deuterium, chloro, fluoro, difluoromethyl, trifluoromethyl, amino, methylamino, or dimethylamino.

19. The method of any one of claims 1 to 12 and 15 to 18, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where the bridged cycloalkyl of R8is bicyclofl. l.l]pentan-l-yl, 3-fluorobicyclo[l.l.l]pentan-l-yl, 3-chlorobicyclo- [1.1.1 ]pentan- 1 -yl, 3 -(hy droxymethyl)-bicyclo[ 1.1.1 ]pentan- 1 -y 1 , 3 - (trifluoromethyl)bicyclo[l .

1. l]pentan-l-yl, 3-(difluoromethyl)-bicyclo[l .

1. l]pentan-l-yl, 3- (methylamino)bicyclo[l.l.l]pentan-l-yl or 3-(dimethylamino)bicyclo[l.l.l]pentan-l-yl and cycloalkyl of R8is cyclobutyl, cyclopropyl, l-(difluoromethyl)cyclobutyl, 1- (trifluoromethyl)cyclobutyl, l-(difluoromethyl)cyclopropyl, or l-(trifluoromethyl)cyclopropyl.

20. The method of any one of claims 1 to 12 and 16 to 19, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Rband Rcare independently selected from hydrogen, alkyl, halo, haloalkyl, hydroxy, and cyano and Rdis selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl (substituted as defined in the first aspect), haloalkyl, amino, alkylamino, dialkylamino, heterocyclyl, phenyl, phenylalkyl, and heteroaryl wherein phenyl, phenylalkyl, heteroaryl, and heterocyclyl are substituted with Re, Rf, and Rg.

21. The method of any one of claims 1 to 12 and 16 to 20, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where Rband Rcare independently selected from hydrogen, methyl, fluoro, chloro, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, hydroxy, and cyano, and Rdis selected from hydrogen, methyl, trideuteromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, amino, dimethylamino, di ethylamino, 3, 3 -difluorocyclobutyl, 4,4-difluorocyclohexyl, 3 -hydroxy-3 -methylcyclobutyl, 3- cyano-3 -methylcyclobutyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydropyran-4-yl, 1,1- di oxidothi etan-3 -yl, l,l-dioxidotetrahydro-2H-thiopyran-4-yl, benzyl, phenyl, pyridin-2-yl, pyri din-3 -yl, and pyridin-4-yl.

22. The method of any one of claims 1 to 11, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R8is haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, amino, alkylamino, dialkylamino, substituted amino, phenyl, phenylalkyl, heteroaryl, or heteroaralkyl wherein phenyl and heteroaryl, either by itself or as part of phenylalkyl and heteroaralkyl, respectively, are substituted with Rh, R1, and Rk.

23. The method of any one of claims 1 to 22, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is -Q-(alk1)ni-SO2R10, -Q1- (alk2)n2-SO(=NRu)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15-Q4-(alk5)n5-CONR16R17, - Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, or heteroaryl, wherein heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, aryl, and heteroaryl are substituted with Rx, Ry, and Ryl.

24. The method of any one of claims 1 to 23, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is -Q-(alk1)ni-SO2R10, -Q1- (alk2)n2-SO(=NRu)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, - Q5-(alk6)n6-NR18COR19, or -Q6-(alk7)n7-NR20SO2R21.

25. The method of any one of claims 1 to 24, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, where each of the aforementioned rings is substituted with Rvand Rw.

26. The method of any one of claims 1 to 25, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is other than bond and each of n1, n2, n3, n4, n5, n6, and n7is 0.

27. The method of any one of claims 1 to 25, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is other than bond and each of n1, n2, n3, n4, n5, n6, and n7is 1.

28. The method of any one of claims 1 to 25 and 27, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where each of alk1, alk2, alk3, alk4, alk5, alk6, and alk7is methylene or ethylene.

29. The method of any one of claims 1 to 23, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, or spiro sulfoximinyl, wherein each aforementioned ring is substituted with Rx, Ry, and Ry.

30. The method of any one of claims 1 to 29, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is where:(1) the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are where the: cycloalkyl is: bridged cycloalkyl isbicvclvl heterocvclvl ALS:respectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and(2) the heterocyclyl, bridged heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, spiro sulfoximinyl, bicyclyl sulfoximinyl, cyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where:bridged heterocyclyl is:cyclylsulfoximinyl is *:bicyclyl sulfoximinyl is:aryl is: heteroaryl is:fused heteroaryl is:respectively, wherein each ring in (2) is substituted as defined therein; and * wherein in each ring in (1) and (2) above, denotes bond to NH of -NHR5moiety in the method of Formula each ring in (1) denotes bond to remainder of -Q-(alk1)ni- SO2R10, -Q1-(alk2)n12, -Q2-(alk3)n3-SO2NR13R14, -Q3-(alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alR19, or -Q6-(alk6)n7-NR20SO2R21.

31. The method of any one of claims 1 to 30, is wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is where:(1) the cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, and heteroaryl of each of Q, Q1, Q2, Q3, Q4, Q5, and Q6are where the: c cloalk l is: bridged cyclolalkyl is:s iro c cloalk l is: heterocyclyf' ISrespectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and(2) the heterocyclyl, spiro heterocyclyl, bridged heterocyclyl, bicyclic heterocyclyl, spiro sulfoximinyl, bicyclyl sulfoximinyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, aryl, heteroaryl, and fused heteroaryl of R5are where: heterocyclyl is:bridged heterocyclyl is:bicyclic heterocyclyl is:cyclylsulfoximinyl is:and bicyclyl sulfoximinyl is:respectively, wherein each ring in (2) is substituted as defined therein; andwherein in each ring in (1) and (2) and in each ring in (1) have the same meaning as claim 30.

32. The method of any one of claims 1 to 31, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is where:(1) the cycloalkyl, bridged cycloalkyl, heterocyclylA, bicyclic heterocyclylA, spiro heterocyclylA, and arespectively, wherein each ring of Q, Q1, Q2, Q3, Q4, Q5, and Q6is substituted as defined therein; and(2) the heterocyclyl, bicyclic heterocyclyl, spiro heterocyclyl, spiro sulfoximinyl, bicyclyl sulfoximinyl, aryl, and heteroaryl of R5are where: heterocyclyl is: bicyclic heterocyclic is: spiro heterocyclyl is:respectively, wherein each ring in (2) is substituted as defined therein; and whereineach ring in (1) and (2); and in each ring in (1) have the same meaning as in claim 57 andin each ring in (2) denotes attachment to one of Rx, Ry, and Ryl.

33. The method of any one of claims 1 to 32, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R11, R18, and R20are methyl, ethyl, or propyl.34, The method of any one of claims 1 to 33, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where:R15and R19are independently selected from alkyl, fluoro, chloro, -CR22=CR23R24, and heterocyclyl substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R10and R21are independently selected from alkyl, cycloalkyl, haloalkyl, fluoro, chloro, - CR22=CR23R24, aryl, aralkyl, heteroaryl, heteroaralkyl, and heterocyclyl wherein cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl;R12is alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or -CR22=CR23R24; andR13, R14, R16, and R17are independently selected from hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and heterocyclyl which is substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano.

35. The method of any one of claims 1 to 34, wherein the compound of Formulae (I) and (le), or a pharmaceutically acceptable salt thereof, is where R5is 3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, 4-(methylsulfonyl)cyclohexyl, 2,2-dioxidohexahydro-lH- cy cl openta[c]thi ophen-5 -yl, l-(methylsulfonyl)piperidin-4-yl, l-(methylaminosulfonyl)-piperidin- 4-yl, l-(aminosulfonyl)piperidin-4-yl, 4-(piperazin-l-yl)phenyl, 4-methylsulfonylphenyl, 4- dimethylaminomethylphenyl, 4-(4-methylpiperazin-l-yl)phenyl, 4-(vinylsulfonyl)phenyl, 4- aminosulfonylphenyl, 4-((2-(dimethylamino)vinyl)sulfonyl)phenyl, l-acetylpiperidin-4-yl, 1- fluorosulfonylpiperidin-4-yl, l-acryloylpiperidin-4-yl, 4-(3-(dimethylamino)acryloyl)phenyl, 4- (vinylsulfonimidoyl)phenyl, l-(3-(diethylamino)-acryloyl)piperidin-4-yl, 1 -(3 -(diisopropyl - amino)acryloyl)piperidin-4-yl, 1 -(2-cyano-3 -(dimethylamino)acryloyl)piperidin-4-yl, 4-(2- (diethylamino)vinyl)sulfonylphenyl, 4-((2-(diethylamino)vinyl)sulfonyl)phenyl, 4-((2- (ethyl(isopropyl)amino)vinyl)sulfonyl)phenyl, l-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-4- yl, 4-(2-(diisopropylamino)vinyl)sulfonylphenyl, 4-((l-cyano-2-(dimethylamino)vinyl)sulfonyl)- phenyl, 2-(methylsulfonyl)-2-azaspiro[3.3]heptan-6-yl, 1 -(methyl sulfonyl)azepan-4-yl, 2- (methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl, 3-(methylsulfonyl)-3-azabicyclo[3.1 ,0]hexan- 6-yl, 2-(((lR,5S,6s)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 2-(((lR,5S,6r)-3- (methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl, 5-(piperazin-l-yl)pyridin-2-yl, 1 -aminosulfonyl - piperidin-4-yl, 1 -methylaminosulfonylpiperidin-4-yl, 1 -(4-(2-methoxy ethyl)piperazin- 1 -yl)-piperidin-4-yl, l-dimethylamino-sulfonylpiperidin-4-yl, 4-piperazin-l-ylphenyl, 1 -piperazin- 1- ylsulfonylpiperidin-4-yl, l-(N-(2-dimethylaminoethyl)-N-methylaminosulfonyl)piperidin-4-yl, 1- (N,N-bis-(hydroxyethyl)aminosulfonyl)piperidin-4-yl, l-(4-methylpiperazin-l-ylsulfonyl)- piperidin-4-yl, l-((2-dimethylaminoethylamino)sulfonyl)-piperidin-4-yl, 2-methylsulfonylethyl, 4- (S-methylsulfonimidoyl)cyclohexyl, l-(methylsulfonyl)piperidin-3-yl, 1 -(methyl sulfonyl)-4, 5,6,7- tetrahydro-lH-indazol-5-yl, 3-(methylsulfonyl)propyl, 4-(piperazin-l-ylsulfonyl)cyclohexyl, 1- (N-(l-methylazeti din-3 -yl)-N-methylaminosulfonyl)piperidin-4-yl, l,l-dioxidotetrahydro-2H- thiopyran-4-yl, 2-aminosulfonylethyl, 1 -imino- 1 -oxidohexahydro- 116-thiopyran-4-yl, 2,2-dioxido- 2-thiaspiro[3.3]heptan-6-yl, 1 -(methylimino)- 1 -oxidohexahydro- 116-thiopyran-4-yl, 1-(N- (azetidin-3-yl)-N-methylaminosulfonyl)piperidin-4-yl, 2-imino-2-oxido-216-thiaspiro[3.3]heptan- 6-yl, (lR,5S,6s)-3,3-dioxido-3-thiabicyclo[3.1.0]hexan-6-yl, (lR,5S,6r)-3,3-dioxido-3- thiabicyclo[3.1 ,0]hexan-6-yl, (4aR,6S)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (4aS,6R)- 1 , 1 -dioxidooctahydropyridof 1 ,2-b] [ 1 ,2,6]thiadiazin-6-yl, (3 aR, 5 s,6aS)-2,2- dioxidohexahydro-lH-cyclopenta[c]thiophen-5-yl, l-(methylsulfonylmethyl)-piperidin-4-yl, 7,7- dioxido-7-thiaspiro[3.5]nonan-2-yl, 4-(4-(2-methoxyethyl)piperazin-l-yl)phenyl, 4-(l- methylpiperazin- 1 -yl)phenyl, 5-(piperazin- 1 -yl)pyridin-2-yl, 1 , 1 -di oxidotetrahydrothi ophen-3 -yl, 2-fluoro-4-methylsulfonylphenyl, 2-methyl-4-methylsulfonylphenyl, ((lr,3r)-3- (methylsulfonyl)cyclobutyl, 3-((methylsulfonyl)methyl)-bicyclo[l .

1. l]pentan-l-yl, 3-(N- methylmethylsulfonamido)bicyclo[l. l.l]pentan-l-yl, 3-((dimethylaminocarbonyl)- methyl)bicyclo[l .

1. l]pentan-l-yl, (lr,3r)-3-(N-methylmethylsulfonamido)cyclobutyl, 3- ((methylsulfonyl)-methyl)bicyclo[l .

1. l]pentan-l-yl, 3-((N,N-dimethylsulfamoyl)methyl)- bicyclo[l. l.l]pentan-l-yl, 2-(methylimino)-2-oxido-216-thiaspiro[3.3]heptan-6-yl, 3- (sulfamoylmethyl)bicyclo[l .

1. l]pentan-l-yl, 3-((S-methylsulfonimidoyl)methyl)- bicyclof 1.1.1 ]pentan- 1 -yl, 1 -aminosulfonylpiperidin-4-yl, 3 -(2-(4-methylpiperazin- 1 -yl)-2- oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 -yl, 3 -(2-(4-,morpholin-4-yl)-2-oxoethyl)bicyclo[ 1.1.1 ]-pentan- 1 - yl, (3R,4S)-3-fluoro-l-(methylsulfonyl)piperidin-4-yl, (3S,4S)-3-fluoro-l-(methylsulfonyl)- piperidin-4-yl, or (3S,4S)-3-methoxy-l-(methylsulfonyl)piperidin-4-yl.

36. The method of any one of claims 1 to 35, wherein the disease is cancer selected from ovarian cancer, endometrial cancer, breast cancer, lung cancer, skin cancer, bladder cancer, cervical cancer, colorectal cancer, cancer of the small intestine, colon cancer, rectal cancer, cancer of the anus, gastric cancer, head and neck cancer, liver cancer, prostate cancer, testicular cancer, uterine cancer, esophageal cancer, gall bladder cancer, pancreatic cancer, stomach cancer, thyroid cancer, and parathyroid cancer.

37. A compound of Formula (IIB):wherein:W is N, CH, or C when attached to R4;X and Z are independently CR6, NR7, N, 0, or S; and Y is CR8, NR9, or N; provided that both of X and Z are not simultaneously O or S; and when each of X and Z is CR6, then Y is other than CR8; each R6is independently hydrogen, alkyl, halo, hydroxyalkyl, or cyano;R7is hydrogen or alkyl;R8is hydrogen, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl other than morpholinyl, tetrahydropyranyl, or pyrrolidinyl, bicyclic heterocyclyl, bridged heterocyclyl, or spiro heterocyclyl;R9is hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, alkylamino, dialkylamino, substituted amino, aminoalkyl, cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, wherein:(A) cycloalkyl, bicyclic cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl of R8and R9are substituted with one or two Raindependently selected from hydrogen, deuterium, alkyl, deuteroalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, alkylamino, and dialkylamino;(B) heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl of R8and R9are substituted with Rb, Rc, and Rdindependently selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl (wherein cycloalkyl, bridged cycloalkyl, and spiro cycloalkyl are substituted with one or two substituents independently selected from hydrogen, alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, hydroxy, cyano, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, heteroaryl, and heteroaralkyl (wherein aryl, by itself or aspart of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl are substituted with Re, Rf, and Rgindependently selected from hydrogen, alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, amino, alkylamino, and dialkylamino);(C) aryl, by itself or as part of aralkyl, and heteroaryl, by itself or as part of heteroaralkyl, of R8and R9are substituted with Rh, R1, and Rkindependently selected from hydrogen, alkyl, deuteroalkyl, cycloalkyl (wherein cycloalkyl is optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxy, and cyano), alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, hydroxy, cyano, amino, alkylamino, dialkylamino, aryl, aralkyl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl, heteroaryl, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, bridged heterocyclyl, and spiro heterocyclyl are substituted with Rm, Rn, and R° independently selected from hydrogen, alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, amino, alkylamino, and dialkylamino); ring RDis phenyl or heteroaryl;R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or cyano;Ar1is cycloalkyl, cycloalkylalkyl, fused cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, bicyclic heterocyclyl, bicyclic heterocyclylalkyl, bridged heterocyclyl, bridged heterocyclylalkyl, fused heterocyclyl, fused heterocyclylalkyl, spiro heterocyclyl, and spiro heterocyclylalkyl (wherein cycloalkyl, by itself or as part of cycloalkylalkyl, fused cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, by itself or as part of bicyclic heterocyclylalkyl, bridged heterocyclyl, by itself or as part of bridged heterocyclylalkyl, fused heterocyclyl, by itself or as part of fused heterocyclylalkyl, and spiro heterocyclyl, by itself or as part of spiro heterocyclylalkyl, are substituted with Rp, Rq, and Rrindependently selected from hydrogen, alkyl, alkoxy, alkylsulfonyl, alkyloxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part ofheterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano)); provided that heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, or spiro heterocyclyl substituted with Rp, Rq, and Rris attached to the -SO2- of -NHSO2- via a carbon ring atom;R4is hydrogen, alkyl, cycloalkyl, cyano, amino, halo, or haloalkyl;R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q3- (alk4)n4-COR15, -Q4-(alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, or fused heteroaryl; wherein: each of Q, Q1, Q2, Q3, Q4, Q5, and Q6is a bond, cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, wherein each of the aforementioned ring is substituted with Rvand Rwindependently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, and cyano; each of n1, n2, n3, n4, n5, n6, and n7is 0 or 1, provided that, when Q is a bond, then each of n1, n2, n3, n4, n5, n6, and n7is 1; each alk1, alk2, alk3, alk4, alk5, alk6, and alk7is alkylene;R11, R18, and R20are hydrogen or alkyl;R10, R12, R15, R19, and R21are independently selected from hydrogen, alkyl, fluoro, chloro, bromo, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, spiro heterocyclyl, heterocyclylalkyl, and -CR22=CR23R24[where R22is hydrogen, alkyl, or cyano, R23is hydrogen or alkyl, and R24is hydrogen, alkyl, halo, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, alkylamino, dialkylamino, -(alkylene)-NR25R26(where R25and R26are independently hydrogen, or alkyl), or heterocyclylalkyl], wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, and spiro heterocyclyl of R10, R12, R15, R19, and R21and heterocyclyl of heterocyclylalkyl of R24are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl; provided R10, R15, R29, and R21are not hydrogen;R13, R14, R16, and R17are independently selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl, and heterocyclylalkyl, wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl, by itself or as part heterocyclylalkyl, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano; and wherein: the cyclylsulfonyl, bicyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, spiro cyclylsulfoximinyl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); or a pharmaceutically acceptable salt thereof; provided that the compound of formula (IIB) is notin the table below:

38. A compound of Formula (IIC 1) wherein:wherein:W is N, CH, or C when attached to R4;R8is alkyl; ring RDis phenyl or heteroaryl;R1, R2, and R3are independently hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or cyano;Ar1is cycloalkyl, cycloalkylalkyl, fused cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, bicyclic heterocyclyl, bicyclic heterocyclylalkyl, bridged heterocyclyl, bridged heterocyclylalkyl, fused heterocyclyl, fused heterocyclylalkyl, spiro heterocyclyl, and spiro heterocyclylalkyl (wherein cycloalkyl, by itself or as part of cycloalkylalkyl, fused cycloalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, by itself or as part of bicyclic heterocyclylalkyl, bridged heterocyclyl, by itself or as part of bridged heterocyclylalkyl, fused heterocyclyl, by itself or as part of fused heterocyclylalkyl, and spiro heterocyclyl, by itself or as part of spiro heterocyclylalkyl, are substituted with Rp, Rq, and Rrindependently selected from hydrogen, alkyl, alkoxy, alkylsulfonyl, alkyloxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, aminoalkyl, aminoalkoxy,aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaryloxy, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part of heteroaryl oxy and heteroaralkyl, and heterocyclyl, by itself or as part of heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkyloxy, are substituted with one, two, or three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano)); provided that heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, or spiro heterocyclyl substituted with Rp, Rq, and Rris attached to the -SO2- of -NHSO2- via a carbon ring atom;R4is hydrogen, alkyl, cycloalkyl, cyano, amino, halo, or haloalkyl;R5is -Q-(alk1)ni-SO2R10, -Q1-(alk2)n2-SO(=NR11)R12, -Q2-(alk3)n3-SO2NR13R14, -Q4- (alk5)n5-CONR16R17, -Q5-(alk6)n6-NR18COR19, -Q6-(alk7)n7-NR20SO2R21, cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, or fused heteroaryl; wherein: each of Q, Q1, Q2, Q4, Q5, and Q6is cycloalkyl, bridged cycloalkyl, spiro cycloalkyl, heterocyclylA, bicyclic heterocyclylA, bridged heterocyclylA, fused heterocyclylA, spiro heterocyclylA, aryl, or heteroaryl, wherein each of the aforementioned ring is substituted with Rvand Rwindependently selected from hydrogen, deuterium, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, and cyano; each of n1, n2, n3, n4, n5, n6, and n7is 0 or 1, provided that, when Q is a bond, then each of n1, n2, n3, n4, n5, n6, and n7is 1; each alk1, alk2, alk3, alk4, alk5, alk6, and alk7is alkylene;R11, R18, and R20are hydrogen or alkyl;R10, R12, R15, R19, and R21are independently selected from hydrogen, alkyl, fluoro, chloro, bromo, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, spiro heterocyclyl, heterocyclylalkyl, and -CR22=CR23R24[where R22is hydrogen, alkyl, or cyano, R23is hydrogen or alkyl, and R24is hydrogen, alkyl, halo, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, alkylamino, dialkylamino, -(alkylene)-NR25R26(where R25and R26are independently hydrogen, or alkyl), or heterocyclylalkyl], wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, heterocyclyl, by itself or as part of heterocyclylalkyl, bicyclic heterocyclyl, bridged heterocyclyl, fused heterocyclyl, and spiro heterocyclyl of R10, R12, R15, R19, and R21and heterocyclyl of heterocyclylalkyl of R24are substituted with one to three substituents independently selected fromhydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cyano, and heterocyclyl; provided R10, R15, R29, and R21are not hydrogen;R13, R14, R16, and R17are independently selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl wherein cycloalkyl, by itself or as part of cycloalkylalkyl, aryl, by itself or as part of aralkyl, heteroaryl, by itself or as part of heteroaralkyl, and heterocyclyl, by itself or as part heterocyclylalkyl, are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, and cyano; and the cyclylsulfonyl, bicyclylsulfonyl, fused cyclylsulfonyl, spiro heterocyclyl, bridged heterocyclyl, cyclylsulfoximinyl, bicyclylsulfoximinyl, spiro sulfoximinyl, and fused heteroaryl of R5are substituted with Rx, Ry, and Rylindependently selected from hydrogen, deuterium, alkyl, alkoxy, alkoxycarbonyl, hydroxy, acyl, halo, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, substituted amino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, aminocarbonyl, aminocarbonylalkyl, cyano, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, aminoalkylamino, cyanoalkyl, cyanoalkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, aralkyl, heteroaryl heteroaryloxy, and heteroaralkyl (wherein aryl, by itself or as part of aralkyl and aryloxy, heteroaryl, by itself or as part, of heteroaryl oxy and heteroaralkyl are substituted with one to three substituents independently selected from hydrogen, alkyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyloxy, alkoxyalkyl, alkoxyalkyloxyalkyl, cyano, and heterocyclyl); or a pharmaceutically acceptable salt thereof; provided the compound of Formula (IIC 1 ) is notare as listed in the table below:

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