Apol1 inhibitors and methods of use

Abstract

Provided herein are compounds of formula (II) or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein n, m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, X9, R6, and R7 are as defined herein. Also provided are methods of preparing compounds of formula (II), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing. Also provided are methods of inhibiting APOL1 and methods of treating an APOL1 -mediated disease, disorder, or condition, such as kidney disease or diabetic retinopathy, in an individual.

Description

APOL1 INHIBITORS AND METHODS OF USE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application 63 / 526,160, filed July 11, 2023, and U.S. Provisional Application 63 / 596,120, filed November 3, 2023, each of which are incorporated by reference herein in their entireities. FIELD OF THE INVENTION

[0002] The disclosure generally relates to APOL1 inhibitors and methods of preparing the same. The disclosure also generally relates to methods of inhibiting APOL1 and methods of treating an APOL1-mediated disease, disorder, or condition in an individual. BACKGROUND OF THE INVENTION

[0003] Apolipoprotein L1 (APOL1) is a pore forming innate immunity factor, protecting individuals from trypanosome parasites (Vanhamme, L. et al. Nature (2003) 422, 83–87). The secreted form of APOL1 circulates in blood as part of distinct high-density lipoprotein (HDL) complexes, known as trypanosome lytic factors (TLFs) (Rifkin, M. R. Proc. Natl. Acad. Sci. USA. (1978) 75, 3450–3454; Raper, J. et al. Infect. Immun. (1999) 67, 1910–1916). TLFs are internalized by the parasites through endocytosis (Hager, K. M. et al. J. Cell Biol. (1994) 126, 155–167). Within trypanosomes, APOL1 forms cation pores, causing ion flux, swelling, and eventual lysis (Rifkin, M. R. Exp. Parasitol. (1984) 58, 81–93; Molina-Portela, M. P. et al. Mol. Biochem. Parasitol. (2005) 144, 218–226; Pérez-Morga, D. et al. Science. (2005) 309, 469–472; Thomson, R. & Finkelstein, A. Proc. Natl. Acad. Sci. USA. (2015) 112, 2894–2899). APOL1 is secreted from the liver as part of an HDL particle that is taken up by T. brucei where it forms a pore that results in lysis of the parasite (Rifkin, M. R. Proc. Natl. Acad. Sci. USA. (1978) 75, 3450-3454; Raper, J. et al. Infect. Immun. (1999) 67, 1910-1916). APOL1 is also expressed in other cell types throughout the body, including endothelial cells and podocytes, where it can be induced by various inflammatory cytokines (Nystrom et al. JAK inhibitor blocks COVID-19 cytokine-induced JAK / STAT / APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids. JCI Insight. 2022 Jun 8;7(11):e157432). APOL1 expressed in cell types outside of liver is thought to be largely intracellular (Cheng et al, J Lipid Res.2015 Aug;56(8):1583-93. doi: 10.1194 / jlr.M059733; Shukha et al, J Am Soc Nephrol.2017 Apr; 28(4): 1079–1083).

[0004] Several Trypanosoma brucei subspecies (T.b. rhodesiense and T.b. gambiense) developed resistance mechanisms to APOL1-dependent killing (Pays, E. et al. Nat. Rev. Microbiol. (2014) 12, 575–584). Positive selection resulted in APOL1 variants, G1 (S342G, I384M) and G2 (N388∆, Y389∆), capable of interfering with these resistance mechanisms (Genovese, G. et al. Science. (2010) 329, 841–845). However, individuals with any binary combination of these variants (G1 / G1, G2 / G2, or G1 / G2), have a greater risk of developing a variety of chronic kidney diseases, including focal segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, human immunodeficiency virus-associated nephropathy (HIVAN) (Genovese, G. et al. Science. (2010) 329, 841–845; Tzur, S. et al. Hum. Genet. (2010) 128, 345-350; Kopp, J. B. et al. J. Am. Soc. Nephrol. (2011) 22, 2129–2137), sickle cell nephropathy (Ashley-Koch, A. E. et al. Br. J. Haematol. (2011) 155, 386–394), lupus nephritis (Freedman, B. I. et al. Arthritis Rheumatol. (2014) 66, 390–396), and an increased rate of Glomerular Filtration Rate (GFR) decline in diabetic kidney disease (Parsa, A. et al. N. Engl. J. Med. (2013) 369, 2183–2196). The APOL1 high-risk genotype has also been associated with COVID-19 associated nephropathy and other viral nephropathies (Shetty, A. et al. J. Am. Soc. Nephrol. (2021) 32, 33–40; Chang, J. H. et al. Am. J. Kidney Dis. (2019) 73, 134–139). Moreover, decreased renal allograft survival has been observed after deceased- donor kidney transplantations from APOL1 high-risk genotype donors (Freedman, B. I. et al. Transplantation. (2016) 100, 194–202). In addition, having two APOL1 risk alleles increases risk for preeclampsia (Reidy, K. J. et al. Am. J. Hum. Genet. (2018) 103, 367–376) and sepsis (Chaudhary, N. S. et al. Clin. J. Am. Soc. Nephrol. (2019) 14, 1733–1740). These variants are predominantly found in individuals of West African descent and partially explain the substantially increased risk of end-stage kidney disease in this population (Genovese, G. et al. Science. (2010) 329, 841-845; Tzur, S. et al. Hum. Genet. (2010) 128, 345-350). These data provided the first evidence that dysregulation of APOL1 activity may cause disease. APOL1 induced kidney disease is thought to be due to pathological effects of intracellular APOL1, likely converging on APOL1 pore formation inside the cell. There are no approved therapies for APOL1-associated nephropathy, andpatients are treated based on the standard of care for their underlying form of chronic kidney disease. This presents a clear unmet need for therapies targeted to people with the APOL1 high-risk genotype.

[0005] Numerous studies have shown that APOL1 risk variants are toxic when overexpressed in human cells (Wan, G. et al. J. Biol. Chem. (2008) 283, 21540–21549; Lan, X. et al. Am. J. Physiol. Renal Physiol. (2014) 307, F326–F336; Olabisi, O. A. et al. Proc. Natl. Acad. Sci. USA. (2016) 113, 830–837; Ma, L. et al. J. Am. Soc. Nephrol. (2017) 28, 1093–1105; Lannon, H. et al. Kidney Int. (2019) 96, 1303–1307). Recent findings suggest that this toxicity is associated with APOL1 pore function (Giovinazzo, J. A. et al. eLife. (2020) 9, e51185). Thus, there is a need to develop compounds suitable for inhibiting APOL1 activity and methods for inhibiting the activity of APOL1 using such compounds.

[0006] Diabetic retinopathy (DR) is a common complication of diabetes and a frequent cause of blindness in this population. Approximately 35% of diabetic patients have some form of retinopathy, which is characterized by retinal microaneurysms, occlusions and neovascularization with attendant loss in visual acuity. Approximately 20% of patients with DR have macular edema (DME) which is a result of fluid leak from the capillary beds into the retina and is associated with more advanced eye disease, including severe vision loss or blindness (Yau, J.W. et al, Meta-Analysis for Eye Disease Study G: Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012;35:556-564). The pathophysiology of retinal microvascular disease in the context of diabetes is complex, but has been associated with higher levels of inflammation, and inflammatory cytokines in the eye (Mason, R.H. et al, Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis. Eye 2022 Jun 7, doi: https: / / doi.org / 10.1038 / s41433-022-02127-x). A locus containing the gene for APOL1 has been reported as a risk factor for DME based on a genetic analysis that provided evidence that an APOL1 missense variant is associated with increased risk for DME (Stockwell, A.D. et al, Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high-risk locus in patients with diabetic macular edema. PLoS Genetics 19(8) (2023): e1010609).

[0007] There are currently no APOL1-targeted therapies for treating eye diseases such as DR and DME. There remains a need for therapies to treat these conditions. BRIEF SUMMARY OF THE INVENTION

[0008] This disclosure describes compounds and compositions that may be useful for the treatment of APOL1-mediated diseases, including a variety of chronic kidney diseases such as FSGS, hypertension-attributed kidney disease, HIVAN, sickle cell nephropathy, lupus nephritis, diabetic kidney disease, viral nephropathy, COVID-19 associated nephropathy, and APOL1- associated nephropathy. The compounds and compositions may treat other APOL1-mediated disorders such as preeclampsia and sepsis. Additionally, for individuals with the APOL1 high-risk genotype, the disclosed compounds and may prevent the onset of non-diabetic renal disease and / or delay the progression of any form of chronic kidney disease. The disclosed chemical matter may also prevent and / or delay progressive renal allograft loss in patients who have received a kidney transplant from a high-risk APOL1 genotype donor.

[0009] This disclosure also describes methods for treating diabetic retinopathies including non- proliferative diabetic retinopathy, proliferative diabetic retinopathy, vision threatening diabetic retinopathy, and diabetic macular edema comprising administration of an APOL1 inhibitor or composition comprising an APOL1 inhibitor. Additionally, the disclosed methods may prevent the onset of diabetic retinopathies and / or delay the progression of diabetic retinopathies. The APOL1 inhibitor may be administered as a single agent or in combination with other agents including, e.g., anti-VEGF agents, Angiopoietin 2 blocking agents, dual VEGF-Angiopoietin 2 blocking agents, corticosteroids, and / or laser therapy.

[0010] A genetic link between a missense variant in APOL1 and DME has been established (Stockwell, A.D. et al, Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high-risk locus in patients with diabetic macular edema. PLoS Genetics 19(8) (2023): e1010609; herein incorporated by reference in its entirety). This variant contains glutamic acid instead of lysine at position 150 (E150 APOL1). E150 APOL1 has been shown to enhance the cytotoxic effects of APOL1 when overexpressed (Lannon et al,Apolipoprotein L1 (APOL1) risk variant toxicity depends on the haplotype background. Kidney International (2019) 96, 1303–1307; herein incorporated by reference in its entirety) and may explain the association of this APOL1 variant with diseases of the eye. APOL1 has been shown to be expressed in various cell types in the eye, including endothelial cells and fibroblasts (Gautam et al. Multi-species single-cell transcriptomic analysis of ocular compartment regulons. Nat Commun. 2021 Sep 28;12(1):5675; herein incorporated by reference in its entirety).

[0011] DME and DR are associated with higher levels of inflammation, and inflammatory cytokines in the eye (Mason, R.H. et al, Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis. Eye 2022 Jun 7, doi: https: / / doi.org / 10.1038 / s41433-022-02127-x; herein incorporated by reference in its entirety). Inflammatory cytokines like interferons, IL-1β and TNF-α are known inducers of APOL1 in endothelial cells (Nichols et al. Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1. Kidney Int.2015 Feb;87(2):332-42; Nystrom et al. JAK inhibitor blocks COVID-19 cytokine-induced JAK / STAT / APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids. JCI Insight.2022 Jun 8;7(11):e157432; each herein incorporated by reference in its entirety). Interferon therapy can lead to retinopathy and macular edema, through mechanisms that remain unclear (Tokai et al. Interferon-associated retinopathy and cystoid macular edema. Arch Ophthalmol. 2001 Jul;119(7):1077-9; Zubir et al. Interferon-α-induced retinopathy in chronic hepatitis C treatment: summary, considerations, and recommendations. Graefes Arch Clin Exp Ophthalmol.2019 Mar;257(3):447-452; each herein incorporated by reference in its entirety). Since interferon is a potent inducer of APOL1, it is plausible that these ocular effects could be driven through interferon mediated induction of APOL1 in eye tissues. In support of this concept, endothelial specific APOL1 expression has been reported to cause vascular leak in mouse models, consistent with the vascular leak seen in DR and DME (Wu et al, APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis. Immunity. 2021 Nov 9; 54(11): 2632–2649.e6; herein incorporated by reference in its entirety).

[0012] A cytotoxic APOL1 variant (E150 APOL1) is genetically associated with diabetic eye disease, and the overexpression of this variant drives toxicity in cellular models. APOL1 isexpressed in the eye in cell types known to be relevant to the pathophysiology of diabetic eye disease including endothelial cells. Therapeutic use of interferon, which induces APOL1 expression in endothelial cells, is also associated with ocular side effects including retinopathy and macular edema. APOL1 induction in mouse models results in vascular leak, consistent with the role of vascular leak in diabetic eye diseases. APOL1 pore blockers have been shown to protect cells from cytotoxicity associated with kidney disease associated variants. Therefore, APOL1 inhibitors as disclosed herein may be therapeutically beneficial in patients with or at risk of DME or DR. Moreover, the APOL1 inhibitors as disclosed herein may be administered by a variety of routes including, e.g., oral administration.

[0013] In one aspect, provided is a compound of formula (II):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, whereinthe C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; either (1) X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein 7the 5-20 membered heteroaryl of R is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more -OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2- Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; (xi) -P(O)(C1-6alkyl)2; or (2) X9is -C-; L3is absent; andone of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or - OH, the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, whereinthe C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1- 6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; or (3) X9is -N-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, whereinthe C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1- 6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1- 6alkoxy, whereinthe C1-6alkyl of R5is optionally substituted with one or more halo or -OH, and the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H or halo; and X5,X6,X7,and X8are each independently N or -CH-, provided that at least one of X5,X6,X7,or X8is N.

[0014] In one aspect, provided herein is a compound of formula (II-A):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n is 1 or 2; and wherein m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, R7, and X9are as defined elsewhere herein. In another variation, n is 1 or 2; and m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7of formula (II-A) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0015] In one aspect, provided herein is a compound of formula (II-B):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: wherein: m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, R6, R7, and X9are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, R6, and R7of formula (II-B) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0016] In one aspect, provided herein is a compound of formula (II-C):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, and X9are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, and R5of formula (II-C) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0017] In one aspect, provided herein is a compound of formula (II-D):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p¸ R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, and X9are as defined elsewhere herein. In another variation, m, p¸ R1, R2, R3, L1, L3, R4, X5, X6, X7, and X8of formula (II-D) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0018] In one aspect, provided herein is a compound of formula (II-E):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, X2, R6, R7, ring A, X5, X6, X7, X8, and X9are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, X2, R6, R7, ring A, X5, X6, X7, and X8of formula (II-E) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0019] In one aspect, provided herein is a compound of formula (II-F):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, R5, ring A, X5, X6, X7, X8, and X9are as defined elsewhere herein. Inanother variation, m, p, R1, R2, R3, L1, R5, ring A, X5, X6, X7, and X8of formula (II-F) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0020] In one aspect, provided herein is a compound of formula (II-G):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, ring A, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, ring A, X5, X6, X7, and X8of formula (II-G) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0021] In one aspect, provided herein is a compound of formula (II-H):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, R1, X2, X3, X4, ring A, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, R1, X2, X3, X4, ring A, X5, X6, X7, and X8of formula (II-H) are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0022] In one aspect, provided is a compound of formula (I):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more C1-6alkyl or deuterium, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either (1) L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more deuterium, – OH, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more deuterium, –OH or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; X1and X2are each independently N or C(R5); andR4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6 alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more – OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, - NH-S(O)2-Ra, or -S(O)2-Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) L3is absent; and onethe other of X1and X2is N or C that is taken together with R , and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)- NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or -OH and the C3-10cycloalkyl of Rbis optionally substituted with one or more - OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more –OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1- 6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more OH or - S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more – OH, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, whereinthe 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, and the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H, halo, or C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halo; and X5,X6,X7,and X8are each independently N or -CH-, provided that at least one of X5,X6,X7,or X8is N.

[0023] Any embodiments provided herein of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, are also embodiments of a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0024] In one aspect, provided herein is a compound of formula (I-A):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n is 1 or 2; and wherein m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7of formula (I-A) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0025] In one aspect, provided herein is a compound of formula (I-B):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: wherein: m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, R6, and R7are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, R6, and R7of formula (I-B) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0026] In one aspect, provided herein is a compound of formula (I-C):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, and R5are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, and R5of formula (I-C) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0027] In one aspect, provided herein is a compound of formula (I-D):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p¸ R1, R2, R3, L1, L3, R4, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, p¸ R1, R2, R3, L1, L3, R4, X5, X6, X7, and X8of formula (I-D) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0028] In one aspect, provided herein is a compound of formula (I-E):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, X2, R6, R7, ring A, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, X2, R6, R7, ring A, X5, X6, X7, and X8of formula (I-E) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0029] In one aspect, provided herein is a compound of formula (I-F):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, R5, ring A, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, R5, ring A, X5, X6, X7, and X8of formula (I-F) are as defined 25for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0030] In one aspect, provided herein is a compound of formula (I-G):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, ring A, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, p, R1, R2, R3, L1, ring A, X5, X6, X7, and X8of formula (I-G) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0031] In one aspect, provided herein is a compound of formula (I-H):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, R1, X2, X3, X4, ring A, X5, X6, X7, and X8are as defined elsewhere herein. In another variation, m, R1, X2, X3, X4, ring A, X5, X6, X7, and X8of formula (I-H) are as defined for a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0032] Any embodiments provided herein of a compound of formula (I) or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, apply where applicable to any other formula detailed herein, the same as if each and every embodiment were specifically and individually listed. Thus, it is understood and described that each embodiment provided herein of a compound of formula (I) or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, such as embodiments related to m, n, p, R1, R2, R3, L1, L2, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7apply to formula (II), (I), (I- A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II- H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the same as if each and every embodiment were specifically and individually listed. It is also understood and described that all such embodiments may be used in any of the pharmaceutical compositions, methods, kits, uses, or other aspects detailed herein.

[0033] In one aspect, provided herein is a pharmaceutical composition, comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula(I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In another variation, provided herein is a pharmaceutical composition, comprising (i) a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0034] In one aspect, provided herein is a method of modulating APOL1 in a cell, comprising exposing the cell to a composition comprising an effective amount of a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-B), (I-C), (I-D), (I-E), (I- F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0035] In one aspect, provided herein is a method of inhibiting APOL1 in a cell, comprising exposing the cell to a composition comprising an effective amount of a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In anothervariation, provided herein is a method of inhibiting APOL1 in a cell, comprising exposing the cell to an effective amount of (i) a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition, comprising a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0036] In one aspect, provided herein is a method of treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the individual is a human.

[0037] In one aspect, provided herein is a method of treating a kidney disease, disorder, or condition in an individual in need thereof, comprising administering to the individual a compound of formula (I), or any variation or embodiment thereof, such as a compound of formula (I-A) (I-B), (I- C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In some embodiments, a therapeutically effective amount of a compound of formula (I) is administered. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II- G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the individual is a human.

[0038] In one aspect, provided herein is a method of treating diabetic retinopathy in an individual in need thereof, comprising administering to the individual a compound of formula (I), or any variation or embodiment thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In some embodiments, a therapeutically effective amount of a compound of formula (I) is administered. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I- C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the individual is a human.

[0039] In one aspect, provided herein is a method of preventing and / or delaying the development of diabetic retinopathy in a subject in need thereof, comprising administering to the subject a compound of formula (I) , or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In one aspect, provided herein is a method of delaying the development of diabetic retinopathy in a subject in need thereof, comprising administering to the subject a compound of formula (I) , or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II- E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0040] In one aspect, provided herein is a kit, comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I- F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof. In another variation, provided herein is a kit, comprising an effective amount of (i) a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition, comprising a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients, and (ii) instructions for use in treating an APOL-1-mediated disease, disorder, or condition in an individual in need thereof. This aspect in some embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II- E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the individual is a human.

[0041] In another variation, provided herein is a kit, comprising (i) a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition, comprising a compound of formula (II), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients, and (ii) instructions for use in treating an APOL-1-mediated disease, disorder, or condition in an individual in need thereof. In some embodiments, the kit comprises a therapeutically effective amount of the compound or pharmaceutical composition. This aspect insome embodiments may employ a compound of any of formulas (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the individual is a human.

[0042] In some aspect, provided herein are methods of preparing a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I-A) (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In another variation, provided herein are methods of preparing a compound of formula (II), or any embodiment or variation thereof, such as a compound of formula (II), (I), (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), (I-H), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0043] All pharmaceutical compositions, methods, kits, uses, or other aspects described herein with reference to formula (I), or a pharmaceutically acceptable salt of any of the foregoing, are also hereby described and embraced for any one of the other formulas detailed herein such as formula (II), the same as if each and every embodiment were specifically and individually listed. BRIEF DESCRIPTION OF THE FIGURES

[0044] FIG. 1 shows the results of an APOL1 E150 G2 mouse transgenic model to validate acute effects of interferon on APOL1 expression in eye retinal tissue.

[0045] FIG. 2 shows the results of an APOL1 E150 G2 mouse transgenic model to validate chronic effects of interferon on APOL1 expression in eye tissue.

[0046] FIG.3A shows a schematic highlighting the administration of IFNγ-AAV and urine / tissue collections.

[0047] FIG.3B shows terminal serum levels of IFNγ from mice.

[0048] FIG.3C shows quantified western blots of normalized APOL1 levels from mouse kidneys.

[0049] FIG.3D shows serum levels of APOL1 from mice dosed with IFNγ-AAV or vehicle (PBS).

[0050] FIG.3E shows urine albumin / creatinine ratio (uACR) in APOL1 G1 / G2 HET mice.

[0051] FIG.3F shows the fold change for kidney injury markers, KIM-1 and NGAL, evaluated by qPCR from mouse kidney tissue homogenates.

[0052] FIG.3G shows PAS staining of mouse kidneys. DETAILED DESCRIPTION OF THE INVENTION

[0053] Unless clearly indicated otherwise, the terms “a,” “an,” and the like, refer to one or more.

[0054] As used herein, “about” a parameter or value includes and describes that parameter or value per se. For example, “about X” includes and describes X per se.

[0055] “Individual” refers to mammals and includes humans and non-human mammals. Examples of individuals include, but are not limited to, some primates and humans. In some embodiments, individual refers to a human.

[0056] As used herein, an “at risk” individual is an individual who is at risk of developing a disease or condition. An individual “at risk” may or may not have a detectable disease or condition, and may or may not have displayed detectable disease prior to the treatment methods described herein. “At risk” denotes that an individual has one or more so-called risk factors, which are measurable parameters that correlate with development of a disease or condition and are known in the art. An individual having one or more of these risk factors has a higher probability of developing the disease or condition than an individual without these risk factor(s).

[0057] “Treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. Beneficial or desired results may include one or more of the following: decreasing one or more symptom resulting from the disease or condition; diminishing the extent ofthe disease or condition; slowing or arresting the development of one or more symptom associated with the disease or condition (e.g., stabilizing the disease or condition, preventing or delaying the worsening or progression of the disease or condition); and relieving the disease, such as by causing the regression of clinical symptoms (e.g., ameliorating the disease state, enhancing the effect of another medication, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival).

[0058] As used herein, “delaying” development of a disease or condition means to defer, hinder, slow, retard, stabilize and / or postpone development of the disease or condition. This delay can be of varying lengths of time, depending on the history of the disease and / or individual being treated. As is evident to one skilled in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease or condition.

[0059] As used herein, the term “therapeutically effective amount” or “effective amount” intends such amount of a compound of the disclosure or a pharmaceutically salt thereof sufficient to effect treatment when administered to an individual. As is understood in the art, an effective amount may be in one or more doses, e.g., a single dose or multiple doses may be required to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved.

[0060] As used herein, “unit dosage form” refers to physically discrete units, suitable as unit dosages, each unit containing a predetermined quantity of active ingredient, or compound, which may be in a pharmaceutically acceptable carrier.

[0061] As used herein, by “pharmaceutically acceptable” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects.

[0062] The term “alkyl”, as used herein, refers to an unbranched or branched saturated hydrocarbon chain. As used herein, alkyl has 1-20 carbons (i.e., C1-20alkyl), 1-16 carbons (i.e., C1-16alkyl), 1-12 carbons (i.e., C1-12alkyl), 1-10 carbons (i.e., C1-10alkyl), 1-8 carbons (i.e., C1-8alkyl), 1- 6 carbons (i.e., C1-6alkyl), 1-4 carbons (i.e., C1-4alkyl), or 1-3 carbons (i.e., C1-3alkyl). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, iso-propyl, n-butyl, sec-butyl, iso- butyl, tert-butyl, pentyl, 2-pentyl, iso-pentyl, neo-pentyl, hexyl, 2-hexyl, 3-hexyl, and 3- methylpentyl. When an alkyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “butyl” includes n-butyl, sec-butyl, iso-butyl, and tert-butyl; and “propyl” includes n-propyl and iso-propyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkyl” group, may be referred to as an “alkylene”.

[0063] The term “alkynyl”, as used herein, refers to a branched or unbranched univalent hydrocarbon chain comprising at least one carbon-carbon triple bond. As used herein, alkynyl has 2-20 carbons (i.e., C2-20alkynyl), 2-16 carbons (i.e., C2-16alkynyl), 2-12 carbons (i.e., C2-12alkynyl), 2-10 carbons (i.e., C2-10alkynyl), 2-8 carbons (i.e., C2-8alkynyl), 2-6 carbons (i.e., C2-6alkynyl), 2-4 carbons (i.e., C2-4alkynyl), or 2-3 carbons (i.e., C2-3alkynyl). Examples of alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, and but-3-ynyl. When an alkynyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “propynyl” includes prop-1-ynyl and prop-2-ynyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkynyl” group, may be referred to as an “alkynylene”.

[0064] The term “alkoxy”, as used herein, refers to an -O-alkyl moiety. As used herein, alkoxy has, for example, 1-6 carbons (i.e., C1-6alkoxy), or 1-3 carbons (i.e., C1-3alkoxy). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy.

[0065] The term “aryl”, as used herein, refers to a fully unsaturated carbocyclic ring moiety. The term “aryl” encompasses monocyclic and polycyclic fused-ring moieties. As used herein, aryl encompasses ring moieties comprising, for example, 6 to 20 annular carbon atoms (i.e., C6-20aryl), 6to 16 annular carbon atoms (i.e., C6-16aryl), 6 to 12 annular carbon atoms (i.e., C6-12aryl), or 6 to 10 annular carbon atoms (i.e., C6-10aryl). Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, fluorenyl, and anthryl.

[0066] The term “cycloalkyl”, as used herein, refers to a saturated or partially unsaturated carbocyclic ring moiety. The term “cycloalkyl” encompasses monocyclic and polycyclic ring moieties, wherein the polycyclic moieties may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl groups, wherein the ring moiety comprises at least one annular double bond. Cycloalkyl includes any polycyclic carbocyclic ring moiety comprising at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, cycloalkyl includes rings comprising, for example, 3 to 20 annular carbon atoms (i.e., a C3-20cycloalkyl), 3 to 16 annular carbon atoms (i.e., a C3-16cycloalkyl), 3 to 12 annular carbon atoms (i.e., a C3-12cycloalkyl), 3 to 10 annular carbon atoms (i.e., a C3-10cycloalkyl), 3 to 8 annular carbon atoms (i.e., a C3-8cycloalkyl), 3 to 6 annular carbon atoms (i.e., a C3-6cycloalkyl), or 3 to 5 annular carbon atoms (i.e., a C3-5cycloalkyl). Monocyclic cycloalkyl ring moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norbomyl, decalinyl, 7,7-dimethyl -bicyclo [2.2.1]heptanyl, and the like. Still further, cycloalkyl also includes spiro cycloalkyl ring moieties, for example, spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro [5.5]undecanyl.

[0067] The term “halo”, as used herein, refers to atoms occupying group VIIA of The Periodic Table and includes fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodo).

[0068] The term “heteroaryl”, as used herein, refers to an aromatic (fully unsaturated) ring moiety that comprises one or more annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heteroaryl” includes both monocyclic and polycyclic fused-ring moieties. As used herein, a heteroaryl comprises, for example, 5 to 20 annular atoms (i.e., a 5-20 membered heteroaryl), 5 to 16 annular atoms (i.e., a 5-16 membered heteroaryl), 5 to 12 annular atoms (i.e., a 5-12 membered heteroaryl), 5 to 10 annular atoms (i.e., a 5-10 membered heteroaryl), 5 to 8 annular atoms (i.e., a 5-8 membered heteroaryl), or 5 to 6 annular atoms (i.e., a 5-6 membered heteroaryl). Any monocyclic or polycyclic aromatic ring moietycomprising one or more annular heteroatoms is considered a heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heteroaryl moiety). Examples of heteroaryl groups include, but are not limited to, acridinyl, benzimidazolyl, benzindolyl, benzofuranyl, benzonaphthofuranyl, benzoxazolyl, benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl, furanyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, triazolyl, tetrazolyl, and triazinyl. Examples of the fused-heteroaryl rings include, but are not limited to, quinolinyl, isoquinolinyl, benzo[b]thiophenyl, indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl, and imidazo[1,5-a]pyridinyl, wherein the heteroaryl can be bound via either ring of the fused system.

[0069] The term “heterocyclyl”, as used herein, refers to a saturated or partially unsaturated cyclic moiety that encompasses one or more annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heterocyclyl” includes both monocyclic and polycyclic ring moieties, wherein the polycyclic ring moieties may be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic ring moiety comprising at least one annular heteroatom is considered a heterocyclyl, regardless of the point of attachment to the remainder of the molecule (i.e., the heterocyclyl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heterocyclyl moiety). Further, the term heterocyclyl is intended to encompass any polycyclic ring moiety comprising at least one annular heteroatom wherein the polycyclic ring moiety comprises at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, a heterocyclyl comprises, for example, 3 to 20 annular atoms (i.e., a 3-20 membered heterocyclyl), 3 to 16 annular atoms (i.e., a 3- 16 membered heterocyclyl), 3 to 15 annular atoms (i.e., a 3-15 membered heterocyclyl), 3 to 12 annular atoms (i.e., a 3-12 membered heterocyclyl), 3 to 10 annular atoms (i.e., a 3-10 membered heterocyclyl), 3 to 8 annular atoms (i.e., a 3-8 membered heterocyclyl), 3 to 6 annular atoms (i.e., a 3-6 membered heterocyclyl), 3 to 5 annular atoms (i.e., a 3-5 membered heterocyclyl), 5 to 8 annularatoms (i.e., a 5-8 membered heterocyclyl), or 5 to 6 annular atoms (i.e., a 5-6 membered heterocyclyl). Examples of heterocyclyl groups include, e.g., azetidinyl, azepinyl, benzodioxolyl, benzo[b][l,4]dioxepinyl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyranonyl, benzofuranonyl, dioxolanyl, dihydropyranyl, hydropyranyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, furanonyl, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2- oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thiophenyl (i.e., thienyl), thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo- thiomorpholinyl. Examples of spiro heterocyclyl rings include, but are not limited to, bicyclic and tricyclic ring systems, such as oxabicyclo[2.2.2]octanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6- azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of fused heterocyclyl rings include, but are not limited to, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3- c]pyridinyl, indolinyl, and isoindolinyl, where the heterocyclyl can be bound via either ring of the fused system.

[0070] The term “oxo”, as used herein, refers to a =O moiety.

[0071] The terms “optional” and “optionally”, as used herein, mean that the subsequently described event or circumstance may or may not occur and that the description includes instances where the event or circumstance occurs and instances where it does not. Accordingly, the term “optionally substituted” infers that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms on the designated atom or moiety or group may be replaced or not replaced by an atom or moiety or group other than hydrogen. By way of illustration and not limitation, the phrase “methyl optionally substituted with one or more chloro” encompasses -CH3, -CH2Cl, -CHCl2, and -CCl3moieties.

[0072] It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments.

[0073] The term “pharmaceutically acceptable salt , as used herein, of a given compound refers to salts that retain the biological effectiveness and properties of the given compound and which are not biologically or otherwise undesirable. “Pharmaceutically acceptable salts” include, for example, salts with inorganic acids, and salts with an organic acid. In addition, if the compounds described herein are obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, may be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. Such compositions are well known in the pharmaceutical art. See, e.g., Handbook of Pharmaceutical Salts Properties, Selection, and Use, International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), which is incorporated herein by reference. Those skilled in the art will recognize various synthetic methodologies that may be used to prepare nontoxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts may be prepared from inorganic or organic acids. Salts derived from inorganic acids include, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include, e.g., acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluene-sulfonic acid, salicylic acid, trifluoroacetic acid, and the like. Likewise, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, aluminum, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines. Specific examples of suitable amines include, by way of example only, isopropylamine, trimethyl amine, diethyl amine, tri(iso-propyl), amine, tri(n-propyl) amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like.

[0074] Isotopically labeled forms of the compounds depicted herein may be prepared. Isotopically labeled compounds have structures depicted herein, except that one or more atoms arereplaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,13N,15N,15O,17O,18O,31P,32P,35S,18F,36Cl,123I, and125I, respectively. In some embodiments, a compound of formula (I) is provided wherein one or more hydrogen is replaced by deuterium or tritium.

[0075] Some of the compounds provided herein may exist as tautomers. Tautomers are in equilibrium with one another. By way of illustration, amide containing compounds may exist in equilibrium with imidic acid tautomers. Regardless of which tautomer is shown and regardless of the nature of the equilibrium among tautomers, the compounds of this disclosure are understood by one of ordinary skill in the art to comprise both amide and imidic acid tautomers. Thus, for example, amide-containing compounds are understood to include their imidic acid tautomers. Likewise, imidic-acid containing compounds are understood to include their amide tautomers.

[0076] Also provided herein are prodrugs of the compounds depicted herein, or a pharmaceutically acceptable salt thereof. Prodrugs are compounds that may be administered to an individual and release, in vivo, a compound depicted herein as the parent drug compound. It is understood that prodrugs may be prepared by modifying a functional group on a parent drug compound in such a way that the modification is cleaved in vivo to release the parent drug compound. The development of prodrug compounds is well known in the pharmaceutical art. See, e.g., Rautio, J., Kumpulainen, H., Heimbach, T. et al. Prodrugs: design and clinical applications. Nat. Rev. Drug. Discov.7, 255–270 (2008), which is incorporated herein by reference.

[0077] The compounds of the present disclosure, or their pharmaceutically acceptable salts, may include an asymmetric center and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- (or as (D)- or (L)- for amino acids). The present disclosure is meant to include all such possible isomers, as well as their racemic and optically pure forms and mixtures thereof in any ratio. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or may be resolved using conventional techniques, for example, chromatography and / or fractional crystallization. Conventional techniques for the preparation / isolation of individualenantiomers include chiral synthesis from a suitable optically pure precursor or the resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC) or chiral supercritical fluid chromatography (SFC). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, unless specified otherwise, it is intended that the present disclosure includes both E and Z geometric isomers. Likewise, cis- and trans- are used in their conventional sense to describe relative spatial relationships.

[0078] A “stereoisomer” refers to a compound made up of the same atoms bonded by the same bonds, but having different three-dimensional structures, which are generally not interchangeable. The present disclosure contemplates various stereoisomers, or mixtures thereof, and includes “enantiomers,” which refers to two stereoisomers whose structures are non-superimposable mirror images of one another. “Diastereomers” are stereoisomers that have at least two asymmetric atoms, but which are not mirror images of each other.

[0079] Where a given structure has potential for cis and trans configuration, and the composition is made up of at least 90%, by weight, dashes or wedges indicate known cis or trans configuration, e.g.,

[0080] Where a given structure has the potential for enantiomeric and / or diastereomeric forms, flat bonds indicate that all stereoisomeric forms may be present, e.g.,.

[0081] Where enantiomeric and / or diastereomeric forms exist of a given structure, the composition is made up of at least 90%, by weight, an asterisk indicates a single enantiomer or diastereomer with unknown relative or absolute stereochemistry, e.g.,.

[0082] Abbreviations used are those conventional in the art and are in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd, hereby incorporated herein by reference in its entirety. The following examples are intended to be illustrative only and not limiting in any way. °C degrees Celsius Ms2O Methanesulfonic anhydride μL microliter m multiplet (NMR) [M+XX]+observed mass mg milligrams AC50 half-maximal activity min minutes concentration AcOH acetic acid mL milliliter AgBF4Silver tetrafluoroborate mmol millimole BBr3 boron tribromide mM millimolar BF3·Et2O borontrifluoride diethyl M molarity or molar etherate (BPin)2 bis(pinacolato)diboron MS mass spectrometry Calc’d calculated MTBE methyl tert-butyl ether Cs2CO3 cesium carbonate n / a not applicableCuI copper iodide N2nitrogen gas d deuterated (NMR solvents) Na2CO3 sodium carbonate dd doublet of doublets (NMR) NaH sodium hydride DAST diethylaminosulfur trifluoride NaHCO3 sodium bicarbonate DBDMH 1,3-dibromo-5,5-dimethyl- NBS N-bromosuccinimide imidazolidine-2,4-dione NCS N-chlorosuccinimide DDQ 2,3-dichloro-5,6-dicyano-1,4- NH4Cl ammonium chloride benzoquinone DMP Dess–Martin periodinane NH4HCO3 ammonium bicarbonate DCE 1,2-dichloroethane NH4OH ammonium hydroxide DCM dichloromethane Na2S2O4sodium hydrosulfite DIEA N,N-diisopropylethylamine Na2SO3 sodium sulfite DME dimethoxyethane Na2SO4sodium sulfate DMA dimethylacetamide NaBO3·4 sodium perborate tetrahydrate H2O DPPF 1,1'- NaNO2 sodium nitrite bis(diphenylphosphino)ferroc ene EC50 half-maximal effective NMO N-methylmorpholine-N-oxide concentration Et2O diethyl ether NMP N-methyl-2-pyrrolidone EtOAc ethyl acetate NMR nuclear magnetic resonance EtOH ethanol NaIO4 sodium periodate Fe iron g grams NaOH sodium hydroxide h hours Pd / C palladium on carbon H hydrogen Pd(dppf)C [1,1′- l2bis(diphenylphosphino)ferrocen e]dichloropalladium(II) H2 hydrogen gas PMBNH2 4-methoxybenzylamine H2O water POCl3phosphorous oxychloride H2O2 hydrogen peroxide PyAOP (7-azabenzotriazol-1- H2SO4sulfuric acid yloxy)tripyrrolidinophosphoniu m hexafluorophosphate HATU hexafluorophosphate azabenz s singlet (NMR) otriazole tetramethyl uronium HCl hydrochloric acid SEMCl 2-(trimethylsilyl)ethoxymethyl chloride HNO3 nitric acid SFC super fluid chromatography HOAc acetic acid SiO2Silica dioxide HPLC high-performance liquid t triplet (NMR) chromatography I2iodine T3P propanephosphonic anhydrideIn vacuo in a vacuum T4P 2,4,6-tributyl-1,3,5,2,4,6- trioxatriphosphinane 2,4,6- trioxide i-PrOH isopropanol TBAF tetrabutylammonium fluoride IUPAC International Union of Pure tBuOK potassium tert-butoxide and Applied Chemistry K2CO3 potassium carbonate TFA trifluoroacetic acid KOAc potassium acetate THF tetrahydrofuran K2OsO4•2 potassium osmate (VI) TEA triethylamine H2O dihydrate LiHMDS lithium TLC thin layer chromatography bis(trimethylsilyl)amide LiOH lithium hydroxide hydrate TMSCN trimethylsilyl cyanide •H2O MeI methyl iodide TsOH•H2p-toluenesulfonic acid O monohydrate MeOH methanol Zn zinc MeCN acetonitrile Zn(CN)2zinc cyanide MeMgBr methyl magnesium bromide MHz megahertz COMPOUNDS

[0083] Provided herein is a compound of formula (II):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either (1) X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, andthe 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6 alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more - OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, - NH-S(O)2-Ra, or -S(O)2-Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6;(x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) X9is -C-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or - OH and the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, whereinRcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; or (3) X9is -N-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, whereinthe 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1- 6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, whereinthe C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, and the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H or halo; and X5, X6, X7, and X8are each independently N or -CH-, provided that at least one of X5, X6, X7, or X8is N.

[0084] Also provided herein is a compound of formula (I):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4;n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more C1-6alkyl or deuterium, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either (1) L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more deuterium, – OH, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, andthe 3-10 membered heterocyclyl is optionally substituted with one or more – OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more – OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2wherein Reis independently at each occurrence H, C1-6alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2- Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2;or (2) L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1- 6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, and wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or -OH, the C3-10cycloalkyl of Rbis optionally substituted with one or more - OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more –OH, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more OH or - S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more – OH, C1-6alkoxy, or C1-6alkyl, whereinthe C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, wherein the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H, halo, or C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halo; andX5,X6,X7,and X8are each independently N or -CH-, provided that at least one of X5,X6,X7,or X8is N.

[0085] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is an integer from 0 to 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0086] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH. In some embodiments, R2is H, C1-3alkyl, C2-6alkynyl, C3-6cycloalkyl, or 3-6 membered heterocyclyl, wherein the C1-3alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-3alkoxy, and the C3-6cycloalkyl of R2is optionally substituted with one or more -OH. In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H. In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C1-6alkyl. In some embodiments, R2is C1-3alkyl. In some embodiments, R2is methyl or ethyl. In some embodiments, R2is methyl. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0087] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0. In some embodiments m is 1. In some embodiments, m is 2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula(II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0088] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo, -CN, C1-6alkoxy or -C1-6alkyl, wherein the C1-6alkoxy or R1is optionally substituted with one or more halo, and wherein the C1-6alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is halo, -CN, C1-3alkoxy, or -C1-3alkyl, wherein the C1-3alkoxy of R1is optionally substituted with one or more halo, and wherein the C1-3alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is selected from the group consisting of Cl and . In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0089] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, p is an integer from 0 to 10. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0090] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R3is C1-6alkyl. In some embodiments, R3is C1-3alkyl. In some embodiments, R3is methyl. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0091] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the ring system bearing (R1)mand R2is a 2-dihydropyrrolopyridinone optionally substituted at one or more of positions 1, 5, and 7. In some embodiments, the 2-dihydropyrrolopyridinone is a 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2- one. In some embodiments, the 2-dihydropyrrolopyridinone is a 1,3-dihydro-2H-pyrrolo[2,3- c]pyridin-2-one. In some embodiments, the 2-dihydropyrrolopyridinone is a 1,3-dihydro-2H- pyrrolo[3,2-b]pyridin-2-one. In some embodiments, the 2-dihydropyrrolopyridinone is a 1,3- dihydro-2H-pyrrolo[3,2-c]pyridin-2-one. In some embodiments, the 2-dihydropyrrolopyridinone ring system is unsubstituted. In some embodiments, the 2-dihydropyrrolopyridinone ring system is substituted at position 1. In some embodiments, the 2-dihydropyrrolopyridinone ring system is substituted at position 5. In some embodiments, the 2-dihydropyrrolopyridinone ring system is substituted at position 7. In some embodiments, the 2-dihydropyrrolopyridinone ring system is substituted at positions 1, and 5. In some embodiments, the 2-dihydropyrrolopyridinone ring system is substituted at positions 5 and 7. In some embodiments, the 2-dihydropyrrolopyridinone ring system is substituted at positions 1, 5, and 7. In some embodiments, positions 1, 5 and 7 are defined as indicated in the structure,. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0092] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the ring system bearing (R1)m and R2is selected from the group consisting of, , , wherein ## represents the point of attachment to theremainder of the molecule. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0093] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the ring bearing (R3)piswherein ## represents the point of attachment to the remainder of the molecule. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0094] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the ring system bearing (R1)m, R2, and (R3)pis selected from the group consisting. In some variations, the embodiments provided hereinalso apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0095] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene optionally substituted with one or more deuterium, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with -OH or C1-6alkoxy. In some embodiments, L1is C1-3alkylene optionally substituted with one or more deuterium, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with -OH or C1-3alkoxy. In some embodiments, L1is methylene. In some embodiments, L1is ethylene. In some embodiments, L1is ethylene optionally substituted with one or more deuterium, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH or C1-3alkoxy. In someembodiments, L1is , wherein # denotes the point of attachment to L2and ## denotes the point of attachment to the remainder of the molecule. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0096] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L2is O or N(Rx), wherein Rxis H or C1-6alkyl. In some embodiments, L2is O or N(Rx), wherein Rxis H or C1-3alkyl. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0097] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L2is O. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0098] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C1-6alkylene of L3is optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, the C3-10cycloalkylof L3is optionally substituted with one or more –OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH. In some embodiments, L3absent. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0099] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing R4is -S(O)2-Ra, 5-20 membered heteroaryl, -N(Rd)2, -NS(O)-(C1-6alkyl)2, -C(O)-N(Re)2, 3-10 membered heterocyclyl, - S(O)(N-C1-6alkyl)-(C1-6alkyl), or -CN. In some embodiments, R4is S(O)2-Ra, 5-10 membered heteroaryl, -N(Rd)2, -NS(O)-(C1-3alkyl)2, -C(O)-N(Re)2, 3-6 membered heterocyclyl, -S(O)(N-C1-3alkyl)-(C1-3alkyl), or -CN. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0100] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C3-10cycloalkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3-10cycloalkyl optionally substituted with one or more -OH, C(O)2-C1-6alkyl, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2,– C(O)-C3-10heterocyclyl or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3-6cycloalkyl optionally substituted with one or more -OH, C(O)2-C1-6alkyl, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3-6cycloalkyl optionally substituted with one or more -OH, C(O)2-C1-3alkyl, -C(O)-NH(C1-3alkyl), -C(O)-N(C1-3alkyl)2, –C(O)-C3-6heterocyclyl, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH. In some variations,the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0101] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is 5-20 membered heteroaryl. In some embodiments, R4is 5-20 membered heteroaryl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is 5-6 membered heteroaryl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is 5-6 membered heteroaryl optionally substituted with one or more C1-3alkyl. In some embodiments, R4is 5-6 membered heteroaryl optionally substituted with one or more methyl. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0102] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -N(Rd)2, wherein each of Rdis independently H, C1-6 alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more –OH, and wherein Rais C1-6alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis independently H, C1-3 alkyl, or -S(O)2-Ra, wherein the C1-3alkyl of Rdis optionally substituted with one or more –OH, and wherein Rais C1-3alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis independently H, C1-6 alkyl, or -S(O)2-Ra, wherein the C1-3alkyl of Rdis optionally substituted with one or more –OH, and wherein Rais methyl. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0103] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis independently H or C1-6 alkyl. In some embodiments, R4is –C(O)-N(Re)2, wherein each of Reis independently H or C1-3 alkyl. In some embodiments, R4is –C(O)-N(Re)2, whereineach of Reis independently H or methyl. In some embodiments, R is –C(O)-NH2. In some embodiments, R4is –C(O)-NH(CH3). In some embodiments, R4is –C(O)-N(CH3)2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0104] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis independently H or 3-10 membered heterocycle, wherein the 3-10 membered heterocycle is optionally substituted with one or more oxo. In some embodiments, R4is –C(O)- N(Re)2, wherein each of Reis independently H or 3-6 membered heterocycle, wherein the 3-6 membered heterocycle is optionally substituted with one or more oxo. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0105] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH- S(O)2-Ra, or -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, wherein Rais methyl. In some variations, the embodiments provided herein also apply to any other applicableformula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0106] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH, oxo or -S(O)2Ra. In some embodiments, R4is 3-7 membered heterocyclyl optionally substituted with one or more C1-6alkyl, - OH, oxo or -S(O)2Ra. In some embodiments, R4is 3-7 membered heterocyclyl optionally substituted with one or more C1-3alkyl, -OH, oxo or -S(O)2Ra. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0107] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -NS(O)-(C1-6alkyl)2.In some embodiments, R4is -NS(O)-(C1-3alkyl)2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0108] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)(N-C1-6alkyl)-(C1- 6alkyl). In some embodiments, R4is -S(O)(N-C1-3alkyl)-(C1-3alkyl). In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0109] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -CN. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such asa compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0110] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -(CH2)qOH, wherein q is an integer from 0-6. R4is -(CH2)qOH, wherein q is an integer from 0-2. In some embodiments, R4is –OH. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0111] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -C(O)-C1-6alkyl. In some embodiments, R4is -C(O)-C1-3alkyl. In some embodiments, R4is -C(O)CH3. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0112] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -P(O)(C1-6alkyl)2. In some embodiments, R4is -P(O)(C1-3alkyl)2. In some embodiments, R4is -P(O)(CH3)2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0113] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, each of X1and X2is independently N or C(R5). In some embodiments, each of X1and X2is N. In some embodiments, each of X1and X2is C(R5). In some embodiments, one of X1and X2is CR5, and the other of X1and X2is N. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof,or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0114] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, one of X1and X2is CR5, and the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl optionally substituted with one or more of Rb. In some embodiments, one of X1and X2is CR5, and the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form a 5-8 membered heterocyclyl optionally substituted with one or more of Rb. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0115] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, - S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or -OH, and the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo. In some embodiments, Rbis, independently at each occurrence, selected from the group consisting of - OH, halo, oxo, C1-3alkyl, -C(O)-C1-3alkyl, -C(O)-NH2, -C(O)-NH(C1-3alkyl), -C(O)-N(C1-3alkyl)2, - S(O)2-Ra, C3-6cycloalkyl, and 3-6 membered heterocyclyl, wherein the C1-3alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-3alkyl, or C3-6cycloalkyl, wherein the C3- 6cycloalkyl of the C1-3alkyl of Rbis further optionally substituted with one or more C1-3alkyl or -OH, and the C3-6cycloalkyl of Rbis optionally substituted with one or more -OH, C3-6cycloalkyl, or C1- 3alkyl, wherein the C1-3alkyl of the C3-6cycloalkyl of Rbis further optionally substituted with one ormore -OH, deuterium or halo. In some embodiments, Rbis selected from the group consisting of - OH, oxo, -S(O)2CH3, and. In some embodiments, Rbis selected from the group consisting of oxo and. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0116] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rbis oxo. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0117] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, one of X1and X2is CR5, and the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heteroaryl. In some embodiments, one of X1and X2is CR5, and the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form a 5-6 membered heteroaryl. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0118] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, one of X1and X2is CR5, and the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heteroaryl optionally substituted with one or more Rc. In some embodiments one of X1and X2is CR5, and the other of X1and X2is C that is taken together withR4, and the atoms to which they are attached, to form a 5-6 membered heteroaryl optionally substituted with one or more Rc. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0119] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rcis independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more OH or -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more –OH, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH. In some embodiments, Rcis independently at each occurrence, selected from the group consisting of halo, C1-3alkyl, -C(O)-C1-3alkyl, -C(O)-NH2, -C(O)-NH(C1-3alkyl), -C(O)-N(C1-3alkyl)2, -S(O)2-Ra, C3-6cycloalkyl, and 3-6 membered heterocyclyl, wherein the C1-3alkyl of Rcis optionally substituted with one or more -S(O)2-C1-3alkyl, the C3-6cycloalkyl of Rcis optionally substituted with one or more –OH, C1-6alkoxy, or C1-3alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-6 membered heterocyclyl of Rcis optionally substituted with one or more -OH, or C1-3alkyl,wherein the C1-3alkyl is further optionally substituted with one or more -OH. In some embodiments, Rcis selected from the group consisting of methyl and In some variations, the embodiments provided herein also apply to any other applicableformula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof,or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0120] In some embodiments of a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rcis independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, - C(O)-NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more OH, - S(O)2-C1-6alkyl, or C1-6alkoxy, and wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, –OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, and the 3- 10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more - OH. In some embodiments, Rcis independently at each occurrence, selected from the group consisting of -CN, halo, C1-3alkyl, -C(O)-C1-3alkyl, -C(O)-NH2, -C(O)-NH(C1-3alkyl), -C(O)-N(C1- 3alkyl)2, -S(O)2-Ra, C3-6cycloalkyl, and 3-6 membered heterocyclyl, wherein the C1-3alkyl of Rcis optionally substituted with one or more OH, -S(O)2-C1-3alkyl, or C1-3alkoxy, and wherein the C1-3alkoxy of the C1-3alkyl of Rcis optionally substituted with one or more halo, the C3-6cycloalkyl of Rcis optionally substituted with one or more halo, –OH, -C(O)NH2, C1-6alkoxy, or C1-3alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-6 membered heterocyclyl of Rcis optionally substituted with one or more -OH, or C1-3alkyl,wherein the C1-3alkyl is further optionally substituted with one or more -OH. In some embodiments, Rcis selected from the group consisting of methyl and

[0121] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1- 6alkyl of R5is optionally substituted with one or more halo, or -OH and wherein the C1-6alkoxy is optionally substituted with one or more halo. In some embodiments, R5is independently at each occurrence, H, halo, -CN, 3-6 membered heterocyclyl, C1-3alkyl, or C1-3alkoxy, wherein the C1-3alkyl of R5is optionally substituted with one or more halo, or -OH and wherein the C1-3alkoxy is optionally substituted with one or more halo. In some embodiments, R5is selected from the group consisting of F and . In some variations, the embodiments provided herein also apply to anyother applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0122] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is H. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0123] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X3is N or C(R6). In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X4is N or C(R7). In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5, X6, X7, and X8are each independently N or -CH-, provided that at least one of X5, X6, X7, or X8is N. In some embodiments, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N. In some variations, the embodiments provided hereinalso apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0124] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R6and R7are each independently H, halo, or C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halo. In some embodiments, R6and R7are each independently H or fluoro. In some embodiments, each of R6and R7is H. In some embodiments, each of R6and R7is fluoro. In some embodiments, one of R6and R7is H and the other of R6and R7is fluoro. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0125] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a bi-substituted phenyl with one group bound at the para position relative to the phenyl’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0126] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a tri-substituted phenyl with two groups bound at a meta, and the para positions relative to the phenyl’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0127] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a tetra-substituted phenyl with three groups bound at the meta, and para positions relative to the phenyl’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0128] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a bi-substituted pyridine with one group bound at the para position relative to the pyridine’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0129] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a tri-substituted pyridine with two groups bound at the meta, and para positions relative to the pyridine’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0130] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a tri-substituted pyridine with two groups bound at the meta, and para positions relative to the pyridine’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0131] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a bi-substituted pyrimidine with two groups bound at the para position relative to the pyrimidine’s attachment to L2. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0132] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heterocycle of the structure In somevariations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0133] In some embodiments of a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heteroaryl selected from the group consisting ofIn some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heteroaryl selected from the group consisting. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0134] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1, L2, and the ring bearing L3, R4, R6, and R7together formsome embodiments, L1, L2, and the ringbearing L3, R4, R6, and R7together form . In some embodiments, L1,2L , and the ring bearing L3, R4, R6, and R7together form. In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1 or 2, and L2is O. In some embodiments, n is 2, and L2is O. In some embodiments, n is 1, and L2is O. In some embodiments, n is 1 or 2, L2is O and R4is S(O)2- Ra. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0135] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, L2is O and each of X1and X2is C(R5), wherein each R5is independently H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy of R5is optionally substituted with one or more halo. In some embodiments, n is 1, p is 0, L2is O and each of X1and X2is C(R5), wherein each R5is independently H. In some embodiments, n is 1, p is 0, L2is O and each of X1and X2is C(R5), wherein one of R5is H and the other of R5is halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy is optionally substituted with one or more halo. In some embodiments, n is 1, p is 0, L2is O and each of X1and X2is C(R5), wherein each R5is independently halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy is optionally substituted with one or more halo. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomerthereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0136] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, L2is O, one of X1and X2is N, and the other of X1and X2is C(R5), wherein R5is H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy of R5is optionally substituted with one or more halo. In some embodiments, n is 1, p is 0, L2is O, one of X1and X2is N, and the other of X1and X2is C(R5), wherein R5is H. In some embodiments, n is 1, p is 0, L2is O, one of X1and X2is N, and the other of X1and X2is C(R5), wherein R5is halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy of R5is optionally substituted with one or more halo. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0137] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, L2is O, and each of X1and X2is N. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0138] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, L2is O, one of X1and X2is C(R5), wherein R5is H, the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form (i) a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, or (ii) a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, and each of R6and R7is H. In some variations, the embodiments provided herein also apply to any otherapplicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0139] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, L2is O, one of X1and X2is C(R5), wherein R5is H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy of R5is optionally substituted with one or more halo, the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form (i) a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, or (ii) a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, and each of R6and R7is H. In some embodiments, n is 1, L2is O, one of X1and X2is C(R5), wherein R5is H, the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form (i) a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, or (ii) a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, and each of R6and R7is H. In some embodiments, n is 1, L2is O, one of X1and X2is C(R5), wherein R5is halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH, and wherein the C1-6alkoxy of R5is optionally substituted with one or more halo, the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form (i) a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, or (ii) a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, and each of R6and R7is H. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0140] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, L2is O, one of X1and X2is N, the other of X1and X2is C that is taken together with R4, and the atoms to which they are attached, to form (i) a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, or (ii) a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, and each of R6and R7is H. In some variations, the embodiments provided herein also apply to any other applicable formula detailed herein, such as a compound of formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0141] In some embodiments of a compound of formula (II), (1) X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more -OH, (iv) - NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH, (v) -C(O)- N(Re)2wherein Reis independently at each occurrence H, C1-6alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3- 10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra, (vii) -S(O)-N(C1-6alkyl)- (C1-6alkyl), (viii) -CN, (ix) -(CH2)qOH, wherein q is an integer from 0-6, (x) -C(O)-C1-6alkyl, or (xi) -P(O)(C1-6alkyl)2; (2) X9is -C-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, - S(O)2-C1-6alkyl, or C3-10cycloalkyl, and wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or -OH and the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, and wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1- 6alkoxy, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more -OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, and wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, and wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, and wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; or (3) X9is -N- ; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more -OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, and wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, and wherein the C1- 796alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, and wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH.

[0142] In some embodiments, X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1- 6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more -OH, (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH, (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or - S(O)2-Ra, (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra, (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl), (viii) -CN, (ix) -(CH2)qOH, wherein q is an integer from 0-6, (x) -C(O)-C1-6alkyl, or (xi) -P(O)(C1-6alkyl)2.

[0143] In some embodiments, X9is -C-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, and wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or -OH and the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, and wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more -OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, and wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, and wherein the C1- 6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, and wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH.

[0144] In some embodiments, X9is -N-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1- 6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more -OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, and wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, and wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, the 3-10 membered heterocyclyl of Rcisoptionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, and wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH.

[0145] In some embodiments of a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either (1) X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, whereinthe C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1- 6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more - OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, - NH-S(O)2-Ra, or -S(O)2-Ra;(vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) X9is -C-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or - OH,the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; or (3) X9is -N-;L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1- 6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence:(i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1- 6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, and the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H or halo; and X5, X6, X7, and X8are each independently N or -CH-, provided that at least one of X5, X6, X7, or X8is N.

[0146] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-A):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n is 1 or 2; and wherein m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, R7, and X9are as defined for formula (II).

[0147] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-B):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: wherein: m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, R6, R7, and X9are as defined for formula (II).

[0148] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-C):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, and X9are as defined for formula (II).

[0149] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-D):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p¸ R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, and X9are as defined for formula (II).

[0150] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-E):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, X2, R6, R7, ring A, X5, X6, X7, X8, and X9are as defined for formula (II).

[0151] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-F):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, R5, ring A, X5, X6, X7, X8, and X9are as defined for formula (II).

[0152] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-G):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, ring A, X5, X6, X7, and X8are as defined for formula (II).

[0153] In some embodiments, provided herein is a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II-H):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, R1, X2, X3, X4, ring A, X5, X6, X7, and X8are as defined for formula (II).

[0154] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, whereinthe C1-6alkyl of R2is optionally substituted with one or more substituents selected from the group consisting of deuterium, halo, -OH, -NH2, and C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl and deuterium, wherein the C1-6alkyl is further optionally substituted with one or more substituents selected from the group consisting of -OH and C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either (1) L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of –OH and C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more substituents selected from the group consisting of deuterium, –OH, and C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of –OH and C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, whereinthe C1-6alkyl of Rdis optionally substituted with one or more – OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl; wherein the 3-10 membered heterocyclyl is optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halo, oxo, -OH, -NH2, -NH- S(O)2-Ra, and -S(O)2-Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, -OH , oxo and -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, whereinthe 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1- 6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more substituents selected from the group consisting of halo, OH, -S(O)2- C1-6alkyl, and C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl and -OH, the C3-10cycloalkyl of Rbis optionally substituted with one or more substituents selected from the group consisting of -OH, C3-10- cycloalkyl, and C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more –OH, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)-NH(C1- 6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more OH or - S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more substituents selected from the group consisting of –OH, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, whereinthe 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more substituents selected from the group consisting of - OH, oxo, =NH, C1-6alkyl, and -S(O2)-C1-6alkyl, wherein the C1-6alkyl of 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of halo, -OH, -S(O)2-C1-6alkyl, and -N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more substituents selected from the group consisting of -OH, -C(O)2-C1-6alkyl, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, and C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more substituents selected from the group consisting of halo and -OH, and wherein the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H, halo, or C1-6alkyl, wherein C1-6alkyl,is optionally substituted with one or more halo; andX5,X6,X7,and X8are each independently N or -CH-, provided that at least one of X5,X6,X7,or X8is N.

[0155] In some embodiments, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (I-A):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n is 1 or 2; and wherein m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7are as defined for formula (I).

[0156] In some embodiments, provided herein is a compound of formula (I) or formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (I-A1):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7are as defined for formula (I).

[0157] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0158] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0159] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0.

[0160] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, p is an integer from 0 to 10. In some embodiments, p is 0 or 1. In some embodiments, p is 0.

[0161] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene. In some embodiments, L1is C1-3alkylene. In some embodiments, L1is ethylene. In some 98embodiments, L1is wherein, # denotes the point of attachment to -O- and ## denotes thepoint of attachment to the remainder of the molecule.

[0162] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0163] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais methyl.

[0164] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, each of X1and X2is C(R5).

[0165] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is H.

[0166] In some embodiments of a compound of formula (I), (I-A) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, each of R6and R7is H.

[0167] In some embodiments, provided herein is a compound of formula (I) or formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (I-A2):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, L3, R4, X1, X2, X5, X6, X7, X8, R6, and R7are as defined for formula (I).

[0168] In some embodiments of a compound of formula (I), (I-A) or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0169] In some embodiments, provided herein is a compound of formula (I) or formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (I-A3):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n is 1 or 2; and wherein m, n, p, R1, R2, R3, L1, X1, X2, X5, X6, X7, X8, R6, R7, and Raare as defined for formula (I).

[0170] In some embodiments of a compound of formula (I), (I-A) or (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0171] In some embodiments, provided herein is a compound of formula (I), (I-A), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-B):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, R5, R6, and R7are as defined as defined for formula (I).

[0172] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-B1):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, R1, R2, L1, L3, R4, X5, X6, X7, X8, R6, and R7are as defined for formula (I).

[0173] In some embodiments of a compound of formula (I), (I-B) or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0174] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0175] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C1-6alkyl. In some embodiments, R2is C1-3alkyl. In some embodiments, R2is methyl.

[0176] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C1-6alkyl optionally substituted with one or more halo, -OH, or C1-6alkoxy. In some embodiments, R2is C1-3alkyl optionally substituted with one or more halo, -OH, or C1-3alkoxy. In some embodiments, R2is ethyl optionally substituted with one or more halo, -OH, -NH2, or C1-3alkoxy.

[0177] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C3-10cycloalkyl optionally substituted with one or more -OH. In some embodiments, R2is C3-6cycloalkyl optionally substituted with one or more -OH.

[0178] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is 3-15 membered heterocyclyl. In some embodiments, R2is 3-6 membered heterocyclyl.

[0179] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m isan integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0. In some embodiments m is 1. In some embodiments, m is 2.

[0180] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl. In some embodiments, R1is Br.

[0181] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is C1-6alkyl. In some embodiments, R1is methyl.

[0182] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is C1-6alkyl, wherein the C1-6alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is methyl, wherein the methyl of R1is optionally substituted with one or more F. In some embodiemtns. R1is.

[0183] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0184] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, p is an integer from 0 to 10. In some embodiments, p is 0.

[0185] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more C1-6alkyl. In some embodiments, L1is C1-3alkylene optionally substituted with one or more C1-3alkyl. In some embodiments, L1is ethylene optionally substituted with one or more C1-6alkyl. In someembodiments, L1is wherein # denotes the point of attachment to -O- and ## denotes thepoint of attachment to the remainder of the molecule.

[0186] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0187] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C1-6alkylene. In some embodiments, L3C1-3alkylene.

[0188] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C3-10cycloalkyl, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more -OH. In some embodiments, L3is C3-8cycloalkyl, wherein the C3-8cycloalkyl of L3is optionally substituted with one or more -OH.

[0189] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is 3-10 membered heterocyclyl. In some embodiments, L3is 3-6 membered heterocyclyl.

[0190] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-6alkyl, wherein the C1-6alkyl of Rais optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or -N(C1-6alkyl)-C(O)-C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl, wherein the C1-3alkyl of Rais optionally substituted with one or more halo, -OH, -S(O)2-C1-3alkyl, or -N(C1-3alkyl)-C(O)-C1-3alkyl.

[0191] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is-S(O)2-Ra, wherein Rais C3-10cycloalkyl. R4is -S(O)2-Ra, wherein Rais C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rais optionally substituted with one or more -OH, C(O)2-C1-6alkyl, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, –C(O)-C3-10heterocyclyl or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3- 6cycloalkyl, wherein the C3-6cycloalkyl of Rais optionally substituted with one or more -OH, C(O)2- C1-6alkyl, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rais optionally substituted with one or more -OH, C(O)2-C1-3alkyl, -C(O)-NH(C1-3alkyl), -C(O)-N(C1-3alkyl)2, –C(O)-C3-6heterocyclyl, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH.

[0192] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais 3-10 membered heterocyclyl. In some embodiments R4is -S(O)2-Ra, wherein Rais 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Rais optionally substituted with one or more C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais 3-6 membered heterocyclyl, wherein the 3-6 membered heterocyclyl of Rais optionally substituted with one or more C1-6alkyl. In some embodiments, wherein R4is -S(O)2-Ra, wherein Rais 3-6 membered heterocyclyl, wherein the 3-6 membered heterocyclyl of Rais optionally substituted with one or more C1-3alkyl.

[0193] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is 5-20 membered heteroaryl. In some embodiments, R4is 5-20 membered heteroaryl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is 5-6 membered heteroaryl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is 5-6 membered heteroaryl optionally substituted with one or more C1-3alkyl. In some embodiments, R4is 5-6 membered heteroaryl optionally substituted with one or more methyl.

[0194] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is-N(Rd)2, wherein each of Rdis independently H, or C1-6alkyl, wherein the C1-6alkyl of Rdis optionally substituted with one or more –OH or -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis independently H, or C1-3 alkyl, wherein the C1- 3alkyl of Rdis optionally substituted with one or more –OH, or -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis independently H, or C1-3alkyl, wherein the C1-3alkyl of Rdis optionally substituted with one or more –OH or -S(O)2-Ra, wherein Rais methyl.

[0195] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis independently H or C1-6 alkyl. In some embodiments, R4is – C(O)-N(Re)2, wherein each of Reis independently H or C1-3alkyl. In some embodiments, R4is – C(O)-N(Re)2, wherein each of Reis independently H or methyl. In some embodiments, R4is –C(O)- NH2. In some embodiments, R4is –C(O)-NH(CH3). In some embodiments, R4is –C(O)-N(CH3)2.

[0196] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or - S(O)2-Ra, wherein Rais methyl.

[0197] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is3-10 membered heterocyclyl optionally substituted with one or more oxo. In some embodiments, R is 3-7 membered heterocyclyl optionally substituted with one or more oxo.

[0198] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -NS(O)-(C1-6alkyl)2.In some embodiments, R4is -NS(O)-(C1-3alkyl)2.

[0199] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)-N(C1-6alkyl)-(C1-6alkyl).

[0200] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -CN.

[0201] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -P(O)(C1-6alkyl)2. In some embodiments, R4is -P(O)(C1-3alkyl)2. In some embodiments, R4is - P(O)(CH3)2.

[0202] In some embodiments, a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1) is selected from the group consisting111,, ,,,stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1) is selected from the group, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt of any of the foregoing.

[0203] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-B2):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: R5is halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH and wherein the C1-6alkoxy is optionally substituted with one or more halo; and m, R1, R2, L1, L3, R4, X5, X6, X7, X8, R6, and R7are as defined for formula (I).

[0204] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0205] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0206] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C1-6alkyl, wherein the C1-6alkyl of R2is optionally substituted with one or more halo, -OH. In some embodiments, R2is C1-3alkyl, wherein the C1-3alkyl of R2is optionally substituted with one or more halo, -OH. In some embodiments, R2is methyl. In some embodiments, R2is ethyl, wherein the ethyl of R2is optionally substituted with one or more halo, -OH.

[0207] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is 1.

[0208] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0209] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0210] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with -OH or C1-6alkoxy. In some embodiments, L1is methylene. In some embodiments, L1is ethylene optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally 1substituted with one or more -OH or C1-6alkoxy. In some embodiments, L is , wherein # denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0211] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0212] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is 3-10 membered heterocyclyl. In some embodiments, L3is 3-6 membered heterocyclyl.

[0213] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl.

[0214] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -N(Rd)2, wherein each of Rdis independently H, C1-6alkyl, or -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis independently H, C1-3 alkyl, or -S(O)2-Ra,wherein Rais C1-3alkyl. In some embodiments, R is -N(Rd)2, wherein each of Rdis independently H, C1-6alkyl, or -S(O)2-Ra, wherein Rais methyl.

[0215] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis independently H or C1-6alkyl. In some embodiments, R4is – C(O)-N(Re)2, wherein each of Reis independently H or C1-3 alkyl. In some embodiments, R4is – C(O)-N(Re)2, wherein each of Reis independently H or methyl. In some embodiments, R4is –C(O)- NH2. In some embodiments, R4is –C(O)-NH(CH3). In some embodiments, R4is –C(O)-N(CH3)2.

[0216] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis independently H or 3-10 membered heterocycle, wherein the 3- 10 membered heterocycle is optionally substituted with one or more oxo. In some embodiments, R4is –C(O)-N(Re)2, wherein each of Reis independently H or 3-6 membered heterocycle, wherein the 3-6 membered heterocycle is optionally substituted with one or more oxo.

[0217] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more oxo, -OH, -NH2, or -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, wherein Rais methyl.

[0218] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is halo. In some embodiments, R5is Cl, or F.

[0219] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is -CN.

[0220] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is C1-6alkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH. In some embodiments, R5is C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted with one or more halo, or –OH. In some embodiments, R5is C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted with one or more fluoro, or -OH. In some embodiments, R5is selected from the group consisting of fluoro.

[0221] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is 3-10 membered heterocyclyl. In some embodiments, R5is 3-6 membered heterocyclyl.

[0222] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is C1-6alkoxy, wherein the C1-6alkoxy is optionally substituted with one or more halo. In some embodiments R5is C1-3alkoxy, wherein the C1-3alkoxy is optionally substituted with one or more halo. In some embodiments, R5is C1-3alkoxy, wherein the C1-3alkoxy is optionally substituted with one or more fluoro.

[0223] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R6and R7are each independently H or halo. In some embodiments, R6and R7are each independently Hor fluoro. In some embodiments, each of R6and R7is H. In some embodiments, one of R6and R7is H and the other of R6and R7is fluoro.

[0224] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-B3):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: each R5is, independently at each occurrence, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or - OH and wherein the C1-6alkoxy is optionally substituted with one or more halo; and m, R1, R2, L1, L3, R4, X5, X6, X7, X8, R6, and R7are as defined for formula (I).

[0225] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0226] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0227] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C1-6alkyl. In some embodiments, R2is methyl.

[0228] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is 0 or 1. In some embodiments, m is 0. In some embodiments m is 1.

[0229] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0230] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0231] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with -OH or C1-6alkoxy. In some embodiments, L1is methylene. In some embodiments, L1is ethylene optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally 1-61substituted with one or more -OH or C alkoxy. In some embodiments, L is , wherein # denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0232] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0233] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C1-6alkylene. In some embodiments, L3is C1-3alkylene.

[0234] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is 3-10 membered heterocyclyl. In some embodiments, L3is 3-6 membered heterocyclyl.

[0235] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl.

[0236] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -N(Rd)2, wherein each of Rdis independently C1-6 alkyl, or -S(O)2-Ra, and wherein Rais C1-6alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis independently C1-3 alkyl, or -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, R4is -N(Rd)2, wherein each of Rdis methyl, or - S(O)2-Ra, wherein Rais methyl.

[0237] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more oxo. In some embodiments R4is –C(O)-N(Re)2, wherein both Retogether with the N to which they are attached are taken together to form a 3-7 membered heterocyclyl, wherein the 3-7 membered heterocyclyl is optionally substituted with one or more oxo.

[0238] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is, independently at each occurrence selected from the group consisting of, halo and C1-6alkyl. In some embodiments, R5is, independently at each occurrence selected from the group consisting of halo and C1-3alkyl. In some embodiments, R5is, independently at each occurrence, selected from the group consisting of F and methyl. In some embodiments, each R5is F. In some embodiments, each R5is methyl.

[0239] In some embodiments, a compound of formula (I-B) is selected from the group, ,, ,, ,, ,, ,, ,, ,,stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, a compound of formula (I-B) is selected from the group consisting ofF2HC F2HCpharmaceutically acceptable salt of any of the foregoing.

[0240] In some embodiments, provided herein is a compound of formula (I), (I-A), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-C):

[0241] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, X8, and R5are as defined elsewhere herein.

[0242] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-C), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-C1):

[0243] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, R1, R2, R3, L1, L3, R4, X5, X6, X7, and X8are as defined for formula (I).

[0244] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0245] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0246] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments m is 1.

[0247] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0248] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0249] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene. In some embodiments, L1is ethylene. In some embodiments, L1iswherein, # denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0250] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0251] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C1-6alkylene. In some embodiments, L3is C1-3alkylene.

[0252] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl.

[0253] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C3-10cycloalkyl. R4is -S(O)2-Ra, wherein Rais C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rais optionally substituted with one or more C1-6alkyl, and wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rais optionally substituted with one or more C1-6alkyl, and wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, R4is -S(O)2-Ra, wherein Rais C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rais optionally substituted with one or more C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH.

[0254] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais 3-10 membered heterocyclyl. In some embodiments R4is -S(O)2-Ra, wherein Rais 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Rais optionally substituted with one or more C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais 3-6 membered heterocyclyl, wherein the 3-6 membered heterocyclyl of Rais optionally substituted with one or more C1-6alkyl. In some embodiments, wherein R4is -S(O)2-Ra, wherein Rais 3-6 membered heterocyclyl, wherein the 3-6 membered heterocyclyl of Rais optionally substituted with one or more C1-3alkyl.

[0255] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis independently H or C1-6alkyl. In some embodiments, R4is – C(O)-N(Re)2, wherein each of Reis independently H or C1-3 alkyl. In some embodiments, R4is – C(O)-N(Re)2, wherein each of Reis independently H or methyl. In some embodiments, R4is –C(O)- NH2. In some embodiments, R4is –C(O)-N(CH3)2. In some embodiments, R4is –C(O)-NH2. In some embodiments, R4is –C(O)-NH(CH3).

[0256] In some embodiments, provided herein is a compound of formula (I), (I-A), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-C2):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: R5is, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, or -OH and wherein the C1-6alkoxy is optionally substituted with one or more halo; m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, and X8are as defined for formula (I).

[0257] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0258] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0259] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments m is 1.

[0260] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0261] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0262] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is C1-6alkyl, wherein the C1-6alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is methyl, wherein the methyl of R1is optionally substituted with one or more F. In some embodiemtns. R1is.

[0263] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene. In some embodiments, L1is ethylene. In some embodiments, L1is wherein,# denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0264] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0265] In some embodiments of a compound formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C1-6alkylene, wherein the C1-6alkylene of L3is optionally substituted with one or more –OH, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, L3is C1-3alkylene, wherein the C1-6alkylene of L3is optionally substituted with one or more –OH, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH.

[0266] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C3-10cycloalkyl, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more -OH. In some embodiments, L3is C3-8cycloalkyl, wherein the C3-8cycloalkyl of L3is optionally substituted with one or more -OH.

[0267] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl.

[0268] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –(CH2)qOH, wherein q is an integer from 0-6. R4is –(CH2)qOH, wherein q is an integer from 0-2. In some embodiments, R4is –OH.

[0269] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -C(O)-C1-6alkyl. In some embodiments, R4is -C(O)-C1-3alkyl. In some embodiments, R4is - C(O)CH3.

[0270] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is C1-6alkyl. In some embodiments, R5is C1-3alkyl. In some embodiments, R5is methyl.

[0271] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is C1-6alkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo. In some embodiments, R5is C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted with one or more halo. In some embodiments, R5is C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted with one or more fluoro. In some embodiments, R5is

[0272] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-C), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is halo. In some embodiments, R5is Cl, or F.

[0273] In some embodiments, provided herein is a compound of formula (I), (I-A), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-D):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, p, R1, R2, R3, L1, L3, R4, X5, X6, X7, and X8are as defined for a compound of formula (I).

[0274] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0275] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0276] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments m is 1.

[0277] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0278] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0279] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is C1-6alkyl, wherein the C1-6alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more F. In some embodiments, R1is methyl, wherein the methyl of R1is optionally substituted with one or more F. In some embodiments, R1is.

[0280] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene optionally substituted with one or more C1-6alkyl. In some embodiments, L1is ethylene optionally substituted with one or more C1-6alkyl. In some embodiments, L1is selected from the group consisting of1wherein, for each L , # denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0281] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is absent.

[0282] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is -O-.

[0283] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C1-6alkylene. In some embodiments, L3is C1-3alkylene.

[0284] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C1-6alkylene, wherein the C1-6alkylene of L3is optionally substituted with one or more –OH, or C1- 6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH. In some embodiments, L3is C1-3alkylene, wherein the C1-3alkylene of L3is optionally substituted with one or more –OH, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH.

[0285] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C3-10cycloalkyl. In some embodiments, L3is C3-8cycloalkyl.

[0286] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-B), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3is C3-10cycloalkyl, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more -OH. In some embodiments, L3is C3-8cycloalkyl, wherein the C3-8cycloalkyl of L3is optionally substituted with one or more -OH.

[0287] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3 is 3-10 membered heterocyclyl. In some embodiments, L3is 3-6 membered heterocyclyl.

[0288] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-3alkyl.

[0289] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –C(O)-N(Re)2, wherein each of Reis H. In some embodiments, R4is –C(O)-NH2.

[0290] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is 3-10 membered heterocyclyl optionally substituted with one or more C1-6 alkyl. In some embodiments, R4is 3-6 membered heterocyclyl optionally substituted with one or more C1-6 alkyl. In some embodiments, R4is 3-6 membered heterocyclyl optionally substituted with one or more C1-3 alkyl. In some embodiments, R4is 3-6 membered heterocyclyl optionally substituted with one or more methyl.

[0291] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is 3-6 membered heterocyclyl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is 3-6 membered heterocyclyl optionally substituted with one or more C1-3alkyl. In some embodiments, R4is 3-6 membered heterocyclyl optionally substituted with one or more methyl.

[0292] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is –(CH2)qOH, wherein q is an integer from 0-6. R4is –(CH2)qOH, wherein q is an integer from 0-2. In some embodiments, R4is –OH.

[0293] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is -N(Rd)2, wherein each of Rdis independently H. In some embodiments, R4is -NH2.

[0294] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-D) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R4is-P(O)(C1-6alkyl)2. In some embodiments, R4is -P(O)(C1-3alkyl)2. In some embodiments, R is - P(O)(CH3)2.

[0295] In some embodiments, provided herein is a compound of formula (I), (I-A) or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-E):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5- 10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, p, R1, R2, R3L1, X2, Rb, Rc, R6, R7, X5, X6, X7, and X8are as defined for formula (I).

[0296] In some embodiments of a compound of formula (I), (I-A), (I-A2), or (I-E), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0297] In some embodiments, provided herein is a compound of formula (I), (I-A) or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-E1):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5- 10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, p, R1, R2, R3, L1, X1, Rb, Rc, R6, R7, X5, X6, X7, and X8are as defined for formula (I).

[0298] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), or (I-E1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0299] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-E) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-E2):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: r is an integer from 0-1; Y1and Y2are each independently C or N, optionally substituted by one or more H or Rb; and m, R1, R2, L1, X2, Rb, X5, X6, X7, and X8are as defined for formula (I); and wherein the dashed line represents a single or double bond.

[0300] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), or (I-E2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0301] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-E) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-E3):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: r is an integer from 0-1; Y1and Y2are each independently C or N, optionally substituted by one or more H or Rb; Rb1is OH; Rb2is H, C1-6alkyl, or C3-10cycloalkyl, wherein the C1-6alkyl of Rb2is optionally substituted with one or more OH; and m, R1, R2, L1, X2, Rb, X5, X6, X7, and X8are as defined for formula (I); and wherein the dashed line represents a single or double bond.

[0302] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), or (I-E3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0303] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-E) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-E4):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: r is an integer from 0-1; Y2, Y3and Y4are each independently C or N, optionally substituted by one or more H or Rc; and m, R1, R2, L1, X2, Rc, X5, X6, X7, and X8are as defined for formula (I); and wherein the dashed line represents a single or double bond.

[0304] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), or (I-E4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0305] In some embodiments, provided herein is a compound of formula (I), (I-A), (I-A2), or (I-E) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-E5):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: r is an integer from 0-1; Y3, Y4and Y5are each independently C or N, optionally substituted by one or more H or Rc; Rc1is OH; Rc2is H, C1-6alkyl, or C3-10cycloalkyl, wherein the C1-6alkyl of Rc2is optionally substituted with one or more OH; and m, R1, R2, L1, X2, Rc, X5, X6, X7, and X8are as defined for formula (I); and wherein the dashed line represents a single or double bond.

[0306] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), or (I-E5), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0307] In some embodiments, a compound of formula (I-E) is selected from the groupFNF O180, ,, ,, ,, ,, ,, ,, ,or tautomer thereof, or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of formula (I-E) is selected from the group consisting ofF2HC N189stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

[0308] In some embodiments, provided herein is a compound of formula (I), (I-A) or (I-A2), (I- E), or (I-E1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-F):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5- 10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, p, R1, R2, R3, L1, R5, Rb, Rc, X5, X6, X7, and X8are as defined for formula (I).

[0309] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-F), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0310] In some embodiments, provided herein is a compound of formula (I), (I-A) or (I-A2), (I- E), (I-E1), or (I-F), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-F1):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5- 10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, R1, R2, L1, Rb, Rc, X5, X6, X7, and X8are as defined for formula (I).

[0311] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0312] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0313] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C1-6alkyl, wherein the C1-6alkyl of R2is optionally substituted with one or more - OH, -NH2, or C1-6alkoxy. In some embodiments, R2is methyl.

[0314] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is C3-10cycloalkyl, wherein the C3-10cycloalkyl of R2is optionally substituted with one or more -OH. In some embodiments, R2is C3-6cycloalkyl, wherein the C3-6cycloalkyl of R2is optionally substituted with one or more -OH.

[0315] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0 or 1. In some embodiments, m is 0. In some embodiments m is 1.

[0316] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0317] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN. In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I- E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more C1-6alkyl. In some embodiments, L1is ethylene, wherein the ethylene of L1is optionally substituted with one or more C1-6alkyl. In some embodiments, L1is, wherein # denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0318] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, wherein Rbis oxo. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, wherein Rbis oxo.

[0319] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more more halo, OH , or - S(O)2-C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein wherein each Rbis independently oxo, or C1-3alkyl, wherein the C1-3alkyl of Rbis optionally substituted with one or more more halo, OH, or -S(O)2-C1-3alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo.

[0320] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -C(O)-NH(C1-6alkyl). In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -C(O)- NH(C1-3alkyl).

[0321] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -C(O)-C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -C(O)-C1-3alkyl.

[0322] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any ofthe foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis - S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -S(O)2-Ra, wherein Rais methyl.

[0323] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rbis optionally substituted with one or more –OH. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rbis optionally substituted with one or more –OH.

[0324] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-10cycloalkyl, wherein the C3- 10cycloalkyl of Rbis optionally substituted with one or more –OH or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rbis optionally substituted with one or more –OH or C1-3alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more.

[0325] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ringwherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0326] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis 3-10 membered heterocyclyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis 3-6 membered heterocyclyl.

[0327] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl. In some embodiments, ring A is a 5-6 membered heteroaryl.

[0328] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C1-6alkyl. In some embodiments ring A is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C1-3alkyl. In some embodiments, ring A is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis methyl. In some embodiments, ring A is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis isopropyl.

[0329] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is , wherein ## represent a point of attachment to the remainder ofthe molecule and the dashed line represents a single or double bond.

[0330] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C1-6alkyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more -OH or –S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, ring A is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C1-3alkyl, wherein the C1- 3alkyl of Rcis optionally substituted with one or more -OH or –S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, ring A is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C1-3alkyl, wherein the C1-3alkyl of Rcis optionally substituted with one or more –S(O)2-Ra, wherein Rais methyl.

[0331] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rcis optionally substituted with one or more –OH. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rcis optionally substituted with one or more –OH.

[0332] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl isoptionally substituted with one or more Rc, wherein one or more Rcis C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rcis optionally substituted with one or more –OH, or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rcis optionally substituted with one or more –OH, or C1-3alkyl. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more.

[0333] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is, wherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0334] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E1), (I-E2), (I- F), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rb, wherein Rbis 3-10 membered heterocyclyl. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rb, wherein Rbis 3-6 membered heterocyclyl.

[0335] In some embodiments, provided herein is a compound of formula (I), (I-A) or (I-A2), (I- E), (I-E1), or (I-F), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-F2):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: R5is halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1- 6alkyl of R5is optionally substituted with one or more halo, or -OH and wherein the C1-6alkoxy is optionally substituted with one or more halo; ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5-10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, R1, R2, L1, Rb, Rc, X5, X6, X7, and X8are as defined for formula (I).

[0336] In some embodiments of a compound of formula (I), (I-A), (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0337] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0338] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments m is 1.

[0339] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0340] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0341] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene. In some embodiments, L1is ethylene.

[0342] In some embodiments, L1is , wherein, for each L1, # denotes the point ofattachment to L2and ## denotes the point of attachment to the remainder of the molecule.

[0343] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, wherein one or more Rbis oxo. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more of Rb, wherein one or more Rbis oxo.

[0344] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl. Insome embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more more halo, OH , or - S(O)2-C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-3alkyl.

[0345] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rbis optionally substituted with one or more –OH or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rbis optionally substituted with one or more –OH or C1-3alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more.

[0346] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ringwherein ## represents a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0347] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rcis optionally substituted with one or more –OH, or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more Rcis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rcis optionally substituted with one or more –OH, or C1-3alkyl. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with one or more Rc, wherein one or more.

[0348] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is, wherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0349] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), (I-F), or (I-F2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is halo. In some embodiments, R5is fluoro.

[0350] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R5is C1-6alkyl. In some embodiments, R5is C1-3alkyl. In some embodiments, R5is methyl. In some embodiments, R5is C1- 6alkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo. In some embodiments, R5is C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted with one or more halo. In some embodiments, R5is C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted 5with one or more fluoro. In some embodiments, R is .

[0351] In some embodiments, a compound of formula (I-F) is selected from the group, ,, ,, ,, ,, ,, ,or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, a compound of formula (I-F) is selected from the group consisting of222stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0352] In some embodiments, provided herein is a compound of formula (I), (I-A) or (I-A2), (I- E1), or (I-E2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-G):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5-10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, p, R1, R2, R3, L1, ring A, X5, X6, X7, and X8are as defined for formula (I).

[0353] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2is H.

[0354] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0 or 1. In some embodiments m is 1.

[0355] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments R1is Cl.

[0356] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is -CN.

[0357] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is C1-6alkyl, wherein the C1-6alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more F. In some embodiments, R1is methyl, wherein the methyl of R1is optionally substituted with one or more F. In some embodiments, R1is methyl. In some embodiments,.

[0358] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1is C1-6alkylene. In some embodiments, L1is C1-3alkylene. In some embodiments, L1is thylene. In some embodiments, L1e is , wherein, for each L1, # denotes the point of attachment to -O- and ## denotes the point of attachment to the remainder of the molecule.

[0359] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more -OH. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein wherein each Rbis independently oxo, or C1- 3alkyl, wherein the C1-3alkyl of Rbis optionally substituted with one or more -OH.

[0360] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo, or C1-6alkyl. In some embodiments, the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or -OH. In some embodiments, each Rbis independently oxo, or C1-3alkyl. In some embodiments the C1-3alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-3alkyl, or C3-6cycloalkyl, wherein the C3-6cycloalkyl of the C1-3alkyl of Rbis further optionally substituted with one or more C1-3alkyl or -OH. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein each Rbis independently oxo.

[0361] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -C(O)-C1-6alkyl. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein one or more of Rbis -C(O)-C1-3alkyl.

[0362] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-10cycloalkyl, wherein the C3-10cycloalkyl of Rbis optionally substituted with one or more –OH. In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rbis optionally substituted with one or more –OH.

[0363] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, Rbis C3-10cycloalkyl optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more –OH. In some embodiments, Rbis C3-6cycloalkyl optionally substituted with one or more -OH, C3-6cycloalkyl, or C1-3alkyl, wherein the C1-3alkyl is further optionally substituted with one or more –OH. In some embodiments,.

[0364] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ringwherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0365] In some embodiments of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rcis independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more -OH or -S(O)2- C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more –OH, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, or C1-6alkyl,wherein the C1-6alkyl is further optionally substituted with one or more -OH. In some embodiments, Rcis independently at each occurrence, selected from the group consisting of halo, C1-3alkyl, -C(O)-C1-3alkyl, -C(O)-NH2, -C(O)-NH(C1- 3alkyl), -C(O)-N(C1-3alkyl)2, -S(O)2-Ra, C3-6cycloalkyl, and 3-6 membered heterocyclyl, wherein the C1-3alkyl of Rcis optionally substituted with one or more -OH or -S(O)2-C1-3alkyl, the C3-6cycloalkylof Rcis optionally substituted with one or more –OH, C1-6alkoxy, or C1-3alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, and wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-6 membered heterocyclyl of Rcis optionally substituted with one or more -OH, or C1-3alkyl,wherein the C1-3alkyl is further optionally substituted with one or more - OH. In some embodiments, Rcis selected from the group consisting of methyl.

[0366] In some embodiments of a compound of formula (I), (I-A) or (I-A2), (I-E), (I-E1), or (I- G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring, wherein ## represents a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0367] In some embodiments, a compound of formula (I-G) is selected from the group consistingstereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0368] In some embodiments, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (I-H):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-10 membered heterocyclyl of ring A is optionally substituted with one or more Rb, and wherein the 5- 10 membered heteroaryl of ring A is optionally substituted with one or more Rc; and m, R1, R5, Rb, Rc, X2,X3, X4, X5,X6, X7, and X8are as defined for formula (I).

[0369] In some embodiments of a compound of formula (I) or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5is N. In some embodiments, X6is N. In some embodiments, X7is N. In some embodiments, X8is N. In some embodiments, X5and X8are each N. In some embodiments, X6and X7are each N. In some embodiments, X5and X7are each N. In some embodiments, X6and X8are each N.

[0370] In some embodiments of a compound of formula (I) or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is halo. In some embodiments, R1is chloro. In some embodiments, R1is C1-6alkyl substituted with one or more halo. In some embodiments, R1is methyl substituted with one or more fluoro. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, X3and X4are each CH. In some embodiments, X2is N. In some embodiments, X2is C(R5). In some embodiments, R5is H. In some embodiments, R5is is C1-6alkyl optionally substituted with one or more halo. In some embodiments, Rbis methyl substituted with one or more fluoro.

[0371] In some embodiments of a compound of formula (I) or (I-H), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is piperidinyl optionally substituted with one or more Rbor pyrazolyl optionally substituted with one or more Rc. In some embodiments, ring A is piperidinyl optionally substituted with one or more Rb. In some embodiments, Rbis oxo. In some embodiments, Rbis C3-10cycloalkyl optionally substituted with one or more -OH or C3-10cycloalkyl. In some embodiments, Rbis cyclobutyl substituted with -OH and methyl. In some embodiments, ring A is pyrazolyl optionally substituted with one or more Rc. In some embodiments, Rcis C3-10cycloalkyl optionally substituted with one or more -OH or C3-10- cycloalkyl. In some embodiments, Rcis cyclobutyl substituted with -OH and methyl.

[0372] In some embodiments, a compound of formula (I) or (I-H) is selected from the group consisting, ,, ,, ,, ,, ,, ,, ,, ,,stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, a compound of formula (I) or (I-H) is selected from the group consisting ofstereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0373] It is to be understood that any variation or embodiment of m, n, p, R1, R2, R3, L1, L2L3, R4, X1, X2, R5, R6, R7, X5, X6, X7, X8, Ra, Rb, Rc, Y1, Y2, and Y3provided herein can be combined 255with every other variation or embodiment of m, n, p, R , R , R3, L , L L3, R , X , X , R5, R6, R7, X5, X6, X7, X8, Ra, Rb, Rc, Y1, Y2, and Y3, the same as if each and every combination had been individually and specifically described. For example, embodiments where m is 1, n is 1, p is 0, R1is Cl, R2is H, L1is ethylene, L2is O, L3is absent, X2is C(R5), R5is CF3, X1is taken together with R4and the atoms to which they are attached to form pyrazolyl, Rcis cyclobutyl substituted with -OH and methyl, X5is N, X6is CH, X7is CH, X8is CH, X3is C(R6), X4is C(R7), R6is H, and R7is H, can be combined to give.

[0374] It is to be understood that any variation or embodiment of m, n, p, R1, R2, R3, L1, L2L3, R4, X1, X2, R5, R6, R7, X5, X6, X7, X8, X9, Ra, Rb, Rc, Y1, Y2, and Y3provided herein can be combined with every other variation or embodiment of m, n, p, R1, R2, R3, L1, L2L3, R4, X1, X2, R5, R6, R7, X5, X6, X7, X8, X9, Ra, Rb, Rc, Y1, Y2, and Y3, the same as if each and every combination had been individually and specifically described. For example, embodiments where m is 1, n is 1, p is 0, R1is CHCF2, R2is H, L1is ethylene, L2is O, L3is absent, X2is C(R5), R5is CF3, X1is taken together with R4and the atoms to which they are attached to form pyrazolyl, Rcis cyclobutyl substituted with -OH and methyl, X5is CH, X6is CH, X7is CH, X8is N, X3is C(R6), X4is C(R7), R6is H, and R7is H, can be combined to give.

[0375] In some embodiments, provided herein is a compound of formula (I), or any variation of embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of Table 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, provided herein is a compound of formula (II), or any variation of embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, wherein the compound is a compound of Table 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. Table 1.259269273278279

[0376] In some embodiments, a compound of formula (II) is selected from the group consisting of 6-chloro-1'-(2-{7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-diaza-3- naphthyloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one;6-chloro-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-diaza-3- naphthyloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- diaza-3-naphthyloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- diaza-3-naphthyloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-indazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3- dihydro-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3- dihydro-1,3-benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-(2-{7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(2-hydroxy-1,1-dimethylethyl)-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,4- dihydro-3,1-benzoxazin-6-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(2-hydroxy-1,1-dimethylethyl)-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,4- dihydro-3,1-benzoxazin-6-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 3-[5-(2-{6-(difluoromethyl)-2-oxo-1',3,5-triazaspiro[indan-1,4'-piperidin]-1'-yl}ethoxy)-7- (trifluoromethyl)-1H-1,3-benzimidazol-1-yl]-1λ⁶-1,1-thietanedione;3-[5-(2-{6-(difluoromethyl)-2-oxo-1',3,7-triazaspiro[indan-1,4-piperidin]-1-yl}ethoxy)-7- (trifluoromethyl)-1H-1,3-benzimidazol-1-yl]-1λ⁶-1,1-thietanedione; 1'-(2-{7-chloro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{8-fluoro-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,4-dihydro-3,1- benzoxazin-6-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)- 1,2,3,4-tetrahydro-6-quinazolinyloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{8-fluoro-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,4-dihydro-3,1- benzoxazin-6-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-fluoro-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-6-(difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3-benzimidazol-5- yloxy}ethyl)-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one;1'-(2-{7-chloro-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3-benzimidazol-5- yloxy}ethyl)-6-(difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-6-difluoromethoxy-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- difluoromethoxy-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(1-mesyl-3-azetidinyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-{2-[1-(1-mesyl-3-azetidinyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)- 1,2,3,4-tetrahydro-6-quinazolinyloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-methoxy-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-methoxy-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-2H-indazol-6- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-2-(trifluoromethoxymethyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-{2-[2-(1-hydroxy-1-methylethyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 3-[5-(2-{6-(difluoromethyl)-2-oxo-1',3,7-triazaspiro[indan-1,4'-piperidin]-1'-yl}ethoxy)-7- (trifluoromethyl)-1H-1,3-benzimidazol-1-yl]-1-azetidinecarboxamide; 6-(difluoromethyl)-1'-(2-{2-(1-hydroxycyclopropyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-1,3a-diaza-6- indenyloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-propionyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy}ethyl)-1',3,4,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{2-(difluoromethoxymethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-(1-fluorocyclopropyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,2,3- benzotriazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{3-fluoro-1-[(trans)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-indazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{3-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- indazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{3-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- indazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-difluoromethoxy-1'-(2-{3-fluoro-1-[(trans)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-indazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-(hydroxymethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 1'-(2-{2-(tert-butoxymethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-(1-hydroxy-1-methylethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-(2-{2-(3-oxetanyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-(2-{3-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- indazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{3-fluoro-1-[(trans)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-indazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{3-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- indazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-(difluoromethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol- 5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{2-(difluoromethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 1'-(2-{2-cyclopropyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 5-(2-{6-(difluoromethyl)-2-oxo-1',3,7-triazaspiro[indan-1,4'-piperidin]-1'-yl}ethoxy)-1-[(cis)-3- hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazole-2-carbonitrile; 6-difluoromethoxy-1'-(2-{2-methoxy-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methoxy-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(1-hydroxy-1-methylethyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{3-methyl-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-1,3-dihydro-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'- piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methoxy-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 1H-1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-(2-{1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,5,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,4,7-tetraazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{1-methyl-2-[(cis)-3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-1H- 1,3-benzimidazol-6-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-2,3- dihydro-1,3-benzoxazolidin-6-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-2,3- dihydro-1,3-benzoxazol-6-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-methyl-2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 5'-(difluoromethyl)-1-(2-((3-((cis)-3-hydroxy-3-methylcyclobutyl)-5-(trifluoromethyl)imidazo[1,5- a]pyridin-7-yl)oxy)ethyl)spiro[piperidine-4,3'-pyrrolo[3,2-b]pyridin]-2'(1'H)-one; (S or R)-5'-(difluoromethyl)-1-(2-((1-(5-oxopyrrolidin-3-yl)-7-(trifluoromethyl)-1H- benzo[d]imidazol-5-yl)oxy)ethyl)spiro[piperidine-4,3'-pyrrolo[3,2-b]pyridin]-2'(1'H)-one; and (R or S)-5'-(difluoromethyl)-1-(2-((1-(5-oxopyrrolidin-3-yl)-7-(trifluoromethyl)-1H- benzo[d]imidazol-5-yl)oxy)ethyl)spiro[piperidine-4,3'-pyrrolo[3,2-b]pyridin]-2'(1'H)-one; or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0377] In some embodiments, a compound of formula (II) is selected from the group consisting of 6-chloro-1'-(2-{7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-diaza-3- naphthyloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one;1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy}ethyl)- 1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-diaza-3-naphthyloxy}ethyl)- 1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-(2-{2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-diaza-3- naphthyloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-diaza-3- naphthyloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{7-fluoro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-1-[3-hydroxy-3-methylcyclobutyl]-1H-indazol-5-yloxy}ethyl)- 1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3-dihydro- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1,3-dihydro- 1,3-benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-(2-{7-fluoro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)- 1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{2-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(2-hydroxy-1,1-dimethylethyl)-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,4-dihydro- 3,1-benzoxazin-6-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(2-hydroxy-1,1-dimethylethyl)-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,4-dihydro- 3,1-benzoxazin-6-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 3-[5-(2-{6-(difluoromethyl)-2-oxo-1',3,5-triazaspiro[indan-1,4'-piperidin]-1'-yl}ethoxy)-7- (trifluoromethyl)-1H-1,3-benzimidazol-1-yl]-1λ⁶-1,1-thietanedione; 3-[5-(2-{6-(difluoromethyl)-2-oxo-1',3,7-triazaspiro[indan-1,4'-piperidin]-1'-yl}ethoxy)-7- (trifluoromethyl)-1H-1,3-benzimidazol-1-yl]-1λ⁶-1,1-thietanedione;1'-(2-{7-chloro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{8-fluoro-2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1,4-dihydro-3,1- benzoxazin-6-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,2,3,4- tetrahydro-6-quinazolinyloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{8-fluoro-2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1,4-dihydro-3,1- benzoxazin-6-yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-fluoro-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)- 6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)- 6-(difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3-benzimidazol-5- yloxy}ethyl)-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1,3-dihydro-1,3-benzimidazol-5- yloxy}ethyl)-6-(difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,4,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-(2-{7-fluoro-2-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- (difluoromethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-(2-{2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-2-methyl-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)- 6-difluoromethoxy-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 1'-(2-{7-chloro-1-[3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzimidazol-5-yloxy}ethyl)-6- difluoromethoxy-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(1-mesyl-3-azetidinyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(1-mesyl-3-azetidinyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-(2-{2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,2,3,4- tetrahydro-6-quinazolinyloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-methoxy-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-methoxy-1'-(2-{1-[3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy}ethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-4-(trifluoromethyl)-2H-indazol-6- yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-(trifluoromethoxymethyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-{2-[2-(1-hydroxy-1-methylethyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 3-(5-{2-[6-(difluoromethyl)-2-oxo-1',3,7-triazaspiro[indan-1,4'-piperidin]-1'-yl]ethoxy}-7- (trifluoromethyl)-1H-1,3-benzimidazol-1-yl)-1-azetidinecarboxamide; 6-(difluoromethyl)-1'-{2-[2-(1-hydroxycyclopropyl)-1-(3-hydroxy-3-methylcyclobutyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-4-(trifluoromethyl)-1,3a-diaza-6- indenyloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-propionyl-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,4,7-tetraazaspiro[indan-1,4'-piperidin]-2-one; 1'-{2-[2-(difluoromethoxymethyl)-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1,3a-diaza-5- indenyloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(1-fluorocyclopropyl)-1-(3-hydroxy-3-methylcyclobutyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,2,3- benzotriazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[3-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[3-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-{2-[3-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-{2-[3-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one;6-(difluoromethyl)-1'-{2-[2-(hydroxymethyl)-1-(3-hydroxy-3-methylcyclobutyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 1'-{2-[2-(tert-butoxymethyl)-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-(1-hydroxy-1-methylethyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-(3-oxetanyl)-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-3-methyl-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[3-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[3-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H- indazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[7-(difluoromethyl)-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-difluoromethoxy-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-indazol-5- yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(difluoromethyl)-1-(3-hydroxy-3-methylcyclobutyl)-7- (trifluoromethyl)-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2- one;1'-{2-[2-cyclopropyl-1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol- 5-yloxy]ethyl}-6-(difluoromethyl)-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 5-{2-[6-(difluoromethyl)-2-oxo-1',3,7-triazaspiro[indan-1,4'-piperidin]-1'-yl]ethoxy}-1-(3-hydroxy- 3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzimidazole-2-carbonitrile; 6-difluoromethoxy-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-methoxy-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy]ethyl}-1',3,5-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-methoxy-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy]ethyl}-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[2-(1-hydroxy-1-methylethyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-3-methyl-2-oxo-7-(trifluoromethyl)- 2,3-dihydro-1H-1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-methoxy-7-(trifluoromethyl)-1H- 1,3-benzimidazol-5-yloxy]ethyl}-1',3,7-triazaspiro[indan-1,4'-piperidin]-2-one; 6-(difluoromethyl)-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-2-methyl-7-(trifluoromethyl)-1H-1,3- benzimidazol-5-yloxy]ethyl}-1',3,4-triazaspiro[indan-1,4'-piperidin]-2-one; 6-chloro-1'-{2-[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzimidazol-5- yloxy...

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A compound of formula (II):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, andthe C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either: (1) X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1- 6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6alkyl, or -S(O)2-Ra, whereinthe C1-6alkyl of Rdis optionally substituted with one or more - OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2wherein Reis independently at each occurrence H, C1-6alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, - NH-S(O)2-Ra, or -S(O)2-Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) X9is -C-; L3is absent; one of X1and X2is N or C(R5); andthe other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or - OH, the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, 619the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; or (3) X9is -N-; L3is absent; one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, whereinthe C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, andthe C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); R6and R7are each independently H or halo; and X5, X6, X7, and X8are each independently N or -CH-, provided that at least one of X5, X6, X7, or X8is N.

2. The compound of claim 1, wherein the compound is a compound of formula (I):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, andthe C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, and the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either (1) L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1- 6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, whereinthe 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6 alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more - OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2wherein Reis independently at each occurrence H, C1-6alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to which they are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, - NH-S(O)2-Ra, or -S(O)2-Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) L3is absent;one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or - OH, the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -C(O)- NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3- 10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH or -S(O)2-C1-6alkyl,the C3-10cycloalkyl of Rcis optionally substituted with one or more -OH, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1- 6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, and the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6);X4is N or C(R7); R6and R7are each independently H or halo; and X5, X6, X7, and X8are each independently N or -CH-, provided that at least one of X5, X6, X7, or X8is N.

3. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X5is N, and X6, X7, and X8are CH.

4. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X6is N, and X5, X7, and X8are CH.

5. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X8is N, and X5, X6, and X7are CH.

6. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L2is -O-, such that the compound is a compound of formula (I-A):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

7. The compound of any of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein n is 1.

8. The compound of any of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2is H.

9. The compound of any of claims 1-7, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m is 0 or 1.

10. The compound of any of claims 1-8 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1is halo or -C1-3alkyl, wherein the C1-3alkyl of R1is optionally substituted with one or more halo.

11. The compound of any of claims 1-9, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein p is 0.

12. The compound of any of claims 1-11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L1is C1-3alkylene, wherein the C1-3alkylene of L1is optionally substituted with one or more deuterium or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with -OH or C1-3alkoxy.

13. The compound of any of claims 1-12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L1is,wherein * denotes the point of attachment to L2and ** denotes the point of attachment to the remainder of the molecule.

14. The compound of any of claims 1-13, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L2is O.

15. The compound of any of claims 1-14, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L3is absent.

16. The compound of any of claims 1-15, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein each of X1and X2is C(R5).

17. The compound of any of claims 1-16, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein one of X1and X2is N and the other is C(R5).

18. The compound of any of claims 1-17, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein one of X1and X2is N or CR5, and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl optionally substituted with one or more of Rb.

19. The compound of claim 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Rbis, independently at each occurrence, selected from the group consisting of oxo and C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rbis optionally substituted with one or more -OH or C1-3alkyl.

20. The compound of any of claims 1-17, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein one of X1and X2is N or CR5, and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heteroaryl optionally substituted with one or more Rc.

21. The compound of claim 20, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein, Rcis independently at each occurrence,selected from the group consisting of C1-3alkyl and C3-6cycloalkyl, wherein the C3- 10cycloalkyl of Rcis optionally substituted with one or more -OH or C1-3alkyl.

22. The compound of any of claims 1-21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R5is independently at each occurrence, H, halo, or C1-3alkyl, wherein the C1-3alkyl of R5is optionally substituted with one or more halo.

23. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from Table 1.

24. A method for preparing a compound of formula (II), as recited in claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, comprises a step of reacting a compound of formula (II’-A):wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R1, if present is, independently at each occurrence selected from the group consisting of halo, -CN, C1-6alkoxy, and C1-6alkyl, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo, and 630the C1-6alkyl of R1is optionally substituted with one or more halo; R2is H, C1-6alkyl, C2-6alkynyl, C3-10cycloalkyl, or 3-15 membered heterocyclyl, wherein the C1-6alkyl of R2is optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy, the C3-10cycloalkyl of R2is optionally substituted with one or more -OH; R3, if present, is C1-6alkyl; and X5,X6,X7,and X8are each independently N or -CH-, provided that at least one of X5,X6,X7,or X8is N; with: a compound of formula (II’-B):wherein: the dashed line represents a single or double bond; Y1is halo, oxo, or a sulfonate ester; L1is C1-6alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-6alkyl, wherein the C1-6alkyl is further optionally substituted with one or more -OH or C1-6alkoxy; L2is O or N(Rx), wherein Rxis H or C1-6alkyl; and either(1) X9is -C-; L3is absent or is O, C3-10cycloalkyl, 3-10 membered heterocyclyl, or C1-6alkylene, wherein the C3-10cycloalkyl of L3is optionally substituted with one or more –OH or C1-6alkyl, the C1-6alkylene of L3is optionally substituted with one or more –OH or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH, and the 3-10 membered heterocyclyl of L3is optionally substituted with one or more –OH or C1-6alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R4is optionally substituted with one or more C1-6alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-6 alkyl, or -S(O)2-Ra, wherein the C1-6alkyl of Rdis optionally substituted with one or more -OH; (iv) -NS(O)-(C1-6alkyl)2, wherein the C1-6alkyl is optionally substituted with one or more –OH; (v) -C(O)-N(Re)2 wherein Reis independently at each occurrence H, C1-6 alkyl, or 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl of Reis optionally substituted with one or more oxo, or both Retogether with the N to whichthey are attached are taken together to form a 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, -NH2, - NH-S(O)2-Ra, or -S(O)2-Ra; (vi) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl, -OH , oxo or -S(O)2Ra; (vii) -S(O)-N(C1-6alkyl)-(C1-6alkyl); (viii) -CN; (ix) -(CH2)qOH, wherein q is an integer from 0-6; (x) -C(O)-C1-6alkyl; or (xi) -P(O)(C1-6alkyl)2; or (2) X9is -C-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-10 membered heterocyclyl or a 5-20 membered heteroaryl, wherein the 5-10 membered heterocyclyl is optionally substituted with one or more Rb, wherein Rbis, independently at each occurrence, selected from the group consisting of -OH, halo, oxo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, whereinthe C1-6alkyl of Rbis optionally substituted with one or more halo, OH, -S(O)2-C1-6alkyl, or C3-10cycloalkyl, wherein the C3-10cycloalkyl of the C1-6alkyl of Rbis further optionally substituted with one or more C1-6alkyl or - OH, the C3-10cycloalkyl of Rbis optionally substituted with one or more -OH, C3-10cycloalkyl, or C1-6alkyl, wherein the C1-6alkyl of the C3-10cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3- 10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, wherein the 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6alkynyl, andthe 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1- 6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; or (3) X9is -N-; L3is absent; and one of X1and X2is N or C(R5); and the other of X1and X2is N or C that is taken together with R4, and the atoms to which they are attached, to form a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of -CN, halo, C1-6alkyl, C1-6alkoxy, -C(O)-C1-6alkyl, -C(O)- NH2, -C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, -S(O)2-Ra, C3-10cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6alkyl of Rcis optionally substituted with one or more - OH, -S(O)2-C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkoxy of the C1-6alkyl of Rcis optionally substituted with one or more halo, the C3-10cycloalkyl of Rcis optionally substituted with one or more halo, -OH, -C(O)NH2, C1-6alkoxy, or C1-6alkyl, wherein the C1-6alkoxy of the C3-10cycloalkyl of Rcis optionally substituted with one or more 3-5 membered heterocycle, whereinthe 3-5 membered heterocycle is optionally substituted with one or more C1-6alkyl or C2-6 alkynyl, the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH, oxo, =NH, C1-6alkyl, or -S(O2)-C1-6alkyl, wherein the C1-6alkyl of the 3-10 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-6alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-6alkyl, or - N(C1-6alkyl)-C(O)-C1-6alkyl; (ii) C3-10cycloalkyl optionally substituted with one or more -OH, -C(O)2-C1-6alkyl, - C(O)-NH(C1-6alkyl), -C(O)-N(C1-6alkyl)2, or –C(O)-C3-10heterocyclyl, or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -OH; (iii) 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl; or (iv) NH(C1-6alkyl); R5is, independently at each occurrence, H, halo, -CN, 3-10 membered heterocyclyl, C1-6alkyl, or C1-6alkoxy, wherein the C1-6alkyl of R5is optionally substituted with one or more halo or -OH, and the C1-6alkoxy of R5is optionally substituted with one or more halo; X3is N or C(R6); X4is N or C(R7); and R6and R7are each independently H or halo;to give a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

25. The method of claim 24, wherein the compound of claim 2 is prepared by a step comprising alkylation of an amine of formula (II’-A) with an alkyl halide, or sulfonate ester compound of formula (II’-B) in the presence of an inorganic base.

26. The method of claim 25, wherein the inorganic base is selected from the group consisting of potassium carbonate and sodium bicarbonate.

27. A pharmaceutical composition, comprising (i) a compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.

28. A method of modulating APOL1 in a cell, comprising exposing the cell to a composition comprising an effective amount of a compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27.

29. A method of inhibiting APOL1 in a cell, comprising exposing the cell to a composition comprising an effective amount of a compound of any of claims 1-23 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27.

30. A method of treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual a compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27.

31. The method of claim 30, wherein the disease, disorder, or condition is a kidney disease or diabetic retinopathy.

32. The method of claim 30, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease, focal segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, human immunodeficiency virus-associated nephropathy (HIVAN), sickle-cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19 associated nephropathy, preeclampsia, and sepsis.

33. The method of any of claims 30-32, wherein the disease, disorder, or condition is a kidney disease.

34. The method of any of claims 28-32, wherein the disease, disorder, or condition is a chronic kidney disease (CKD).

35. The method of claim 30, wherein the disease, disorder, or condition is diabetic retinopathy.

36. The method of claim 35, wherein the diabetic retinopathy is selected from the group consisting of non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, vision threatening diabetic retinopathy, and diabetic macular edema.

37. The method of claim 35 or 36, wherein the administration comprises oral administration or intravitreal injection.

38. The method of claim 37, wherein the administration comprises oral administration.

39. The method of claim 37, wherein the administration comprises intravitrael injection.

40. The method of any of claims 35-39, further comprising administration of an anti-VEGF agent, an Angiopoietin 2 blocking agent, a dual VEGF-Angiopoietin 2 blocking agent, a corticosteroid, or laser therapy to the individual.

41. A method of delaying the development of an APOL1-mediated disease, disorder, or condition, comprising administering a compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27, to an individual who is at risk of developing an APOL1-mediated disease, disorder, or condition.

42. The method of claim 41, wherein the APOL1-mediated disease, disorder, or condition is a kidney disease or diabetic retinopathy.

43. The method of claim 41 or 42, wherein the APOL1-mediated disease, disorder, or condition is a kidney disease.

44. The method of any of claims 41-43, wherein the APOL1-mediated disease, disorder, or condition is a chronic kidney disease.

45. The method of claim 41, wherein the APOL1-mediated disease, disorder, or condition is selected from the group consisting of chronic kidney disease, focal segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, human immunodeficiency virus-associated nephropathy (HIVAN), sickle-cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19 associated nephropathy, preeclampsia, and sepsis.

46. The method of claim 41 or 42, wherein the APOL-1 mediated disease, disorder, or condition is diabetic retinopathy.

47. The method of claim 46, wherein the diabetic retinopathy is selected from the group consisting of non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, vision threatening diabetic retinopathy, and diabetic macular edema.

48. The method of claim 46 or 47, wherein the administration comprises oral administration or intravitreal injection.

49. The method of claim 48, wherein the administration comprises oral administration.

50. The method of claim 48, wherein the administration comprises intravitreal injection.

51. The method of any of claims 46-50, further comprising administration of an anti-VEGF agent, an Angiopoietin 2 blocking agent, a dual VEGF-Angiopoietin 2 blocking agent, a corticosteroid, or laser therapy to the individual.

52. The method of any of claims 28-51, wherein the individual has an APOL1 mutation.

53. The method of claim 52, wherein the APOL1 mutation is a gain-of-function mutation.

54. The method of any of claims 30-53, wherein a therapeutically effective amount of a compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27, is administered.

55. A kit, comprising (i) a compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27, and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof.

56. The kit of claim 55, wherein the disease, disorder, or condition is a kidney disease or diabetic retinopathy.

57. The kit of claim 55 or 56, wherein the disease, disorder, or condition is a kidney disease.

58. The kit of any of claims 55-57, wherein the disease, disorder, or condition is a chronic kidney disease (CKD).

59. The kit of any of claims 55-58, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease, focal segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, human immunodeficiency virus-associated nephropathy (HIVAN), sickle-cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19 associated nephropathy, preeclampsia, and sepsis.

60. The kit of claim 55, wherein the disease, disorder, or condition is diabetic retinopathy.

61. The kit of claim 60, wherein the diabetic retinopathy is selected from the group consisting of non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, vision threatening diabetic retinopathy, and diabetic macular edema.

62. The kit of claim 60 or 61, wherein the administration comprises oral administration or intravitreal injection.

63. The kit of claim 62, wherein the administration comprises oral administration.

64. The kit of claim 62, wherein the administration comprises intravitreal injection.

65. The kit of any of claims 60-63, further comprising instructions for administration of an anti- VEGF agent, an Angiopoietin 2 blocking agent, a dual VEGF-Angiopoietin 2 blocking agent, a corticosteroid, or laser therapy to the individual.

66. The kit of any of claims 55-65, wherein the individual has an APOL1 mutation.

67. The kit of claim 66, wherein the APOL1 mutation is a gain-of-function mutation.

68. The method of any one of claims 30-54, or the kit of any one of claims 55-67, wherein the individual is a human.

69. Use of the compound of any one of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27, in the preparation of a medicament for treating an APOL1-mediated disease, disorder, or condition.

70. A compound of any one of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 27, for use in treating an APOL1-mediated disease, disorder, or condition.

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