Methods of using APOL1 inhibitors

Abstract

Provided herein are methods of treating diabetic retinopathy in a subject, comprising administering to the subject a compound of formula (I): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, n, p, R1, R2, R3, L1, L2, L3, R4, X1, X2, X3, and X4 are as defined herein.

Description

Docket No.: 79275-20025.40 METHODS OF USING APOL1 INHIBITORS CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application Serial No.63 / 469,344, filed May 26, 2023, which is hereby incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION

[0002] 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).

[0003] APOL1 is an innate immune effector whose main known function is to suppress infection by Trypanosoma brucei, the cause of Human African Trypanosomiasis (Vanhamme, L. et al. Nature (2003) 422, 83-87). 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 signalingny-27345411Docket No.: 79275-20025.40 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] Missense variants G1 (S342G, I384M) and G2 (N388∆, Y389∆) in APOL1 that provide enhanced protection to T. brucei substrains have been associated with an increased risk of specific forms of kidney disease including, e.g., 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). 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.

[0005] 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

[0006] This disclosure 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. Theny-27345412Docket No.: 79275-20025.40 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.

[0007] 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. medRxiv preprint, 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).

[0008] 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 hasny-27345413Docket No.: 79275-20025.40 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).

[0009] 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 is expressed 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 developing DME or DR. Moreover, the APOL1 inhibitors as disclosed herein may be administered by a variety of routes including, e.g., oral administration.

[0010] In one aspect, provided herein is a method of treating diabetic retinopathy in a subject in need thereof, comprising administering to the subject 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;ny-27345414Docket No.: 79275-20025.40 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, 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, and 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, 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,ny-27345415Docket No.: 79275-20025.40 (v) -C(O)-N(Re)2wherein Reis independently at each occurrence H, C1-6alkyl, or 3-10 membered heterocycle, wherein the 3-10 membered heterocycle 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 - 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 whereinny-27345416Docket No.: 79275-20025.40 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 -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and 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.ny-27345417Docket No.: 79275-20025.40

[0011] In some embodiments of the compound of formula (I), the compound is a compound ofstereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n, m, p, R1, R2, R3, R4, R5, R6, R7, L1, L3, X1, X2, X3, X4, and ring A are as defined elsewhere herein.ny-27345418Docket No.: 79275-20025.40

[0012] 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). 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).

[0013] Articles of manufacture are also provided, wherein the article of manufacture comprises a compound of formula (I), such as a compound of formula (I-A), (I-B), (I-C), (I-D), (I-E), (I-F), (I-G), or (I-H), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in a suitable container. Also provided herein are articles of manufacture, comprising a pharmaceutical composition comprising a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in a suitable container. The container may be a vial, jar, ampoule, preloaded syringe, or intravenous bag. BRIEF DESCRIPTION OF THE FIGURES

[0014] 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.

[0015] 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. DETAILED DESCRIPTION OF THE INVENTION

[0016] Unless clearly indicated otherwise, the terms “a,” “an,” and the like, refer to one or more.

[0017] 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.

[0018] “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.

[0019] 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,ny-27345419Docket No.: 79275-20025.40 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).

[0020] “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 of the 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).

[0021] 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.

[0022] 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.

[0023] 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.

[0024] 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.ny-273454110Docket No.: 79275-20025.40

[0025] 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”.

[0026] The term “alkoxy”, as used herein, refers to an -O-alkyl moiety. 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.

[0027] 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), 6 to 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.

[0028] 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.ny-273454111Docket No.: 79275-20025.40 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.

[0029] 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).

[0030] 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 moiety comprising 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.

[0031] 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 leastny-273454112Docket No.: 79275-20025.40 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 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 annular atoms (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.

[0032] 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, theny-273454113Docket No.: 79275-20025.40 phrase “methyl optionally substituted with one or more chloro” encompasses -CH3, -CH2Cl, - CHCl2, and -CCl3moieties.

[0033] It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments.

[0034] 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.

[0035] Isotopically labeled forms of the compounds depicted herein may be prepared. Isotopically labeled compounds have structures depicted herein, except that one or more atomsny-273454114Docket No.: 79275-20025.40 are replaced 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), or formula (I) is provided wherein one or more hydrogen is replaced by deuterium or tritium.

[0036] 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.

[0037] 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.

[0038] 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 individual enantiomers include chiral synthesis from a suitable optically pure precursor or the resolution of the racemate (or the racemate of a salt or derivative) using, forny-273454115Docket No.: 79275-20025.40 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.

[0039] 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 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.

[0040] Where enantiomeric and / or diastereomeric forms exist of a given structure, flat bonds indicate that all stereoisomeric forms of the depicted structure may be present, e.g.,.

[0041] Where enantiomeric forms exist of a given structure, flat bonds and the presence of a “ * ” symbol indicate that the composition is made up of at least 90%, by weight, of a single isomer with unknown absolute stereochemistry,example, with reference to the compounds in Table 1, Compound 122 may represent (S)-5-chloro-1'-[2-({3- oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one, and Compound 123 may represent (R)-5-chloro-1'-[2-({3-oxo- 1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one. Alternatively, Compound 122 may represent (R)-5-chloro-1'-[2-({3-oxo- 1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one, and Compound 123 may represent (S)-5-chloro-1'-[2-({3-oxo- 1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one. In some variations, the asterisk denotes a stereocenter having an (R)ny-273454116Docket No.: 79275-20025.40 configuration. In other variations, the asterisk denotes a stereocenter having an (S) configuration.

[0042] Where enantiomeric and / or diastereomeric forms exist of a given structure with two or more stereocenters, flat bonds and the presence of two or more “ * ” symbols indicate the composition is made up of at least 90%, by weight, of a single enantiomer or diastereomer with unknown absolute stereochemistry,

[0043] Where enantiomeric and / or diastereomeric forms exist of a given structure, the composition is made up of at least 90%, by weight, dashes or wedges indicate a single enantiomer or diastereomer with known relative or absolute stereochemistry, e.g .

[0044] 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,

[0045] 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 Ac2O acetic anhydride μL microliter AIBN azobisisobutyronitrile PWmicrowaveapp apparent (NMR) [M+XX]+observed mass br broad (NMR) AC50half-maximal activity BH3·THF borane-tetrahydrofuran complex concentration BBr3boron tribromideny-273454117Docket No.: 79275-20025.40 BnCl benzyl chloride (Ir[dF(CF [4,4′-Bis(1,1-dimethylethyl)- B(Pin)2bis(pinacolato)diboron3)ppy]2(dt 2,2′-bipyridine-N1,N1′]bis[3,5- Calc’d calculated bpy))PF6difluoro-2-[5-(trifluoromethyl)- Cbz-Cl benzyl chloroformate 2-pyridinyl-N]phenyl- CCl4carbontetrachloride C]Iridium(III) CDI carbonyldiimidazole hexafluorophosphate CHCl3chloroform IUPAC International Union of Pure and CO2carbon dioxide Applied Chemistry Cs2CO3cesium carbonateJ-coupling value (NMR) CuI copper iodide K2CO3potassium carbonate d deuterated (NMR solvents) KI potassium iodide d doublet (NMR) KOAc potassium acetate dd doublet of doublets (NMR) KOH potassium hydroxide DAST diethylaminosulfur trifluoride LiAlH4lithium aluminum hydride DMA N,N-dimethylacetamide LiHMDS lithium bis(trimethylsilyl)amide DCE 1,2-dichloroethane LiOH lithium hydroxide DCM dichloromethane MeOH methanol DIAD diisopropyl azodicarboxylate MeCN acetonitrile DIEA N,N-diisopropylethylamine MHz megahertz DME dimethoxyethane m multiplet (NMR) DMEDA N,N-dimethylethylenediamine mg milligrams DMA dimethylacetamide min minutes DMF N,N-dimethylformamide mL milliliter DPPF 1,1'- mmol millimole bis(diphenylphosphino)ferrocene mM millimolar EC50half-maximal effective M molarity or molar concentration m-CPBA meta-chloroperoxybenzoic acid EDCI 1-ethyl-3-(3- MeCN acetonitrile dimethylaminopropyl)carbodiim MeSO2Na sodium methanesulfinate ide MS mass spectrometry Et3N triethyl amine MsCl methanesulfonyl chloride EtOAc ethyl acetate Ms2O methanesulfonic anhydride EtOH ethanol MTBE methyl tert-butyl ether g grams n / a not applicable h hours NaBH(O sodium triacetoxyborohydride H hydrogen Ac)3H2hydrogen gas NaH sodium hydride H2O water NBS N-bromosuccinimide H2O2hydrogen peroxide NH4ammonium HATU N-[(Dimethylamino)-1H-1,2,3- NH4OH ammonium hydroxide triazolo-[4,5-b]pyridin-1- NH4HCO3ammonium bicarbonate ylmethylene]-N- Na2SO4sodium sulfate methylmethanaminium NaBH3C sodium cyanoborohydride hexafluorophosphate N-oxide N HCl hydrochloric acid NMP 1-methyl-2-pyrrolidinone HOBt hydroxybenzotriazole NMR nuclear magnetic resonance HPLC high-performance liquid NaIO4sodium periodate chromatography NaOH sodium hydroxide In vacuo in a vacuum OsO4osmium tetraoxideny-273454118Docket No.: 79275-20025.40 Pd / C palladium on carbon SFC super fluid chromatography PCy3tricyclohexylphosphine SOCl2thionyl chloride Pd2(dba)3tris(dibenzylideneacetone)dipall t triplet (NMR) adium(0) T3P propanephosphonic acid Pd(PPh3)2bis(triphenylphosphine)palladiu anhydride m(I) chloride TBAB tetrabutylammonium bromide Pd(dba)3tris(dibenzylideneacetone)dipall TBAI tetrabutylammonium iodide adium(0) TEA triethylamine pH potential of hydrogen TFA trifluoroacetic acid PPh3triphenyl phosphine THF tetrahydrofuran PSI pounds per square inch TMSCl trimethylsilyl chloride s singlet (NMR) Xantphos 4,5-bis(diphenylphosphino)-9,9- SEMCl (2- dimethylxanthene chloromethoxyethyl)trimethylsil Zn(CN)2zinc cyanide ane METHODS OF TREATMENT

[0046] In one aspect, provided herein is a method of treating diabetic retinopathy in a subject in need thereof, comprising administering to the subject an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In some embodiments, 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. In some embodiments, a therapeutically effective amount of the APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient is administered. In some embodiments, the administration comprises oral administration or intravitreal injection. In some embodiments, the administration comprises oral administration. In some embodiments, the administration comprises intravitreal injection. In some embodiments, the method further comprises 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 subject.

[0047] In one aspect, provided herein is a method of treating or alleviating diabetic retinopathy in a subject, comprising administering to the subject a compound of formula (I):ny-273454119Docket No.: 79275-20025.40or 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, 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, and 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,ny-273454120Docket No.: 79275-20025.40 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 heterocycle, wherein the 3-10 membered heterocycle 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); andny-273454121Docket No.: 79275-20025.40 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, 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 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 -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and 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,ny-273454122Docket No.: 79275-20025.40 (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. In some embodiments of the 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, 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, 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. In some embodiments, the administration comprises oral administration or intravitreal injection. In some embodiments, the administration comprises oral administration. In some embodiments, the administration comprises intravitreal injection. In some embodiments, the method further comprises 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 subject.

[0048] In one aspect, provided herein is a method of preventing and / or delaying the development of diabetic retinopathy in a subject, comprising administering to the subject a compound of formula (I). In one aspect, provided herein is a method of delaying the development of diabetic retinopathy in a subject, comprising administering to the subject a compound of formula (I). In some embodiments of the 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, 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, the diabetic retinopathy is selected from the group consisting of non-proliferative diabetic retinopathy,ny-273454123Docket No.: 79275-20025.40 proliferative diabetic retinopathy, vision threatening diabetic retinopathy, and diabetic macular edema. In some embodiments, the administration comprises oral administration or intravitreal injection. In some embodiments, the administration comprises oral administration. In some embodiments, the administration comprises intravitreal injection. In some embodiments, the method further comprises 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 subject.

[0049] In some embodiments of the methods described herein, the method comprises administering to the subject a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In some embodiments, a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient is administered. In some embodiments of the 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, the compound is a compound of Table 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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. In some embodiments R1is Cl. In some embodiments, R1is Br. In some embodiments, R1is F.ny-273454124Docket No.: 79275-20025.40

[0054] 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 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, R1is.

[0055] 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 -CN.

[0056] 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 C1-6alkoxy, wherein the C1-6alkoxy of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkoxy, wherein the C1-3alkoxy of R1is optionally substituted with one or more halo. In some embodiments, R1is C1-3alkoxy, wherein the C1-3alkoxy of R1is optionally substituted with one or more F. In some embodiments, R1is methoxy, wherein the methoxy of R1is optionally substituted with one or more F. In some embodiments, R1is.

[0057] 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.

[0058] In some embodiments of a compound of formula (I), 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 embodients R2is methyl or ethyl. In some embodiments, R2is methyl.

[0059] 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 optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-6alkoxy. In some embodiments, R2is C1-3alkyl optionally substituted with one or more deuterium, halo, -OH, -NH2, or C1-3alkoxy. In some embodiments, R2is methyl. In some embodiments, R2is ethyl optionally substituted with one or more halo, -OH, -NH2, or C1-6alkoxy. In some embodiments, R2is selected from the group consisting of.ny-273454125Docket No.: 79275-20025.40

[0060] 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 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. In some embodiments, R2is.

[0061] 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 3-15 membered heterocyclyl. In some embodiments, R2is 3-6 membered heterocyclyl. In some embodiments, R2

[0062] 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.

[0063] 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 (R1)mand R2is a 2-indolinone optionally substituted at one or more of positions 1, 5, and 7. In some embodiments, the 2-indolinone ring is unsubstituted. In some embodiments, the 2-indolinone ring is substituted at position 1. In some embodiments, the 2-indolinone ring is substituted at position 5. In some embodiments, the 2-indolinone ring is substituted at position 7. In some embodiments, the 2-indolinone ring is substituted at positions 1, and 5. In some embodiments, the 2-indolinone ring is substituted at positions 5 and 7. In some embodiments, the 2-indolinone ring is substituted at positions 1, 5, and 7. In some embodiments positions 1, 5 and 7 are defined as indicated in the structure, , wherein position 1 is a N atom, each of positions 5 and 7 is a C atom, and ## represent the point of attachment to the remainder of the molecule.

[0064] 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 (R1)mand R2is selected from the group consisting of, , ,ny-273454126Docket No.: 79275-20025.40

[0065] 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)pis selected from the group consisting, and,, wherein ## represents the point of attachment to the remainder of the molecule.

[0066] 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 (R1)m, R2, and (R3)pis selected from the group consistingny-273454127Docket No.: 79275-20025.40the ring bearing (R1)m, R2, and (R3)pis selected from the group consistingselected from the group consistingsome embodiments, the ring bearingsome embodiments, the ring bearingny-273454128Docket No.: 79275-20025.40

[0067] 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 deuterieum, 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 some embodiments, L1is selected from the group consisting ofwherein, for each L1, # denotes the point of attachment to L2and ## denotes the point of attachment to the remainder of the molecule.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] 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 O.

[0072] 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 C1-6alkylene, whereinny-273454129Docket No.: 79275-20025.40 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. In some embodiments, L3is selected from the group consisting of

[0073] 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 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. In some embodiments, L3is selected from the group consisting of,

[0074] 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, L3 is 3-10 membered heterocyclyl. In some embodiments, L3is 3-6 membered heterocyclyl. In some embodiments, L3 ,

[0075] 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 C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais C1-6alkyl 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 optionally substituted with one or more halo, -OH, -S(O)2-C1-3alkyl, or -N(C1-3alkyl)-C(O)-C1-3alkyl. In some embodiments, R4isny-273454130Docket No.: 79275-20025.40 selected from the group consisting.

[0076] 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 embodiments, R4is selected from the group consisting

[0077] 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 3-10 membered heterocyclyl. In some embodiments R4is -S(O)2-Ra, wherein Rais 3-10 membered heterocyclyl optionally substituted with one or more C1-6alkyl. In some embodiments, R4is -S(O)2-Ra, wherein Rais 3-6 membered heterocyclyl optionally substituted with one or more C1-6alkyl. In some embodiments, wherein R4is -S(O)2-Ra, wherein Rais 3-6 memberedny-273454131Docket No.: 79275-20025.40 heterocyclyl optionally substituted with one or more C1-3alkyl. In some embodiments, R4is.

[0078] 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 embodiments, R4is selected

[0079] In some embodiments of a compound of formula (I), 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, C1-6alkyl, 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, C1-3alkyl, 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, C1-6alkyl, or -S(O)2-Ra, wherein the C1-3alkyl of Rdis optionally substituted with one or more -OH, and wherein Rais methyl. In some embodiments, R4is selected from the group consisting of -NH2,,

[0080] 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 C1-6alkyl. 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.ny-273454132Docket No.: 79275-20025.40

[0081] 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 embodiments, R4is selected from the group consisting

[0082] 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 embodiments, R4is selected from the

[0083] 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 memberedny-273454133Docket No.: 79275-20025.40 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 embodiments, R4is selected from the group consisting

[0084] 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 embodiments,

[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, R4is -CN.

[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, 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 embodiments, R4is selected from the group consisting of,

[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, R4is -C(O)-C1-6alkyl. In some embodiments, R4is -C(O)-C1-3alkyl. In some embodiments, R4is -C(O)CH3.

[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, R4is -P(O)(C1-6alkyl)2. In some embodiments, R4is -P(O)(C1-3alkyl)2.

[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, each of X1and X2isny-273454134Docket No.: 79275-20025.40 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.

[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, 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.

[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, 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 or more -OH, deuterium or halo. In some embodiments, Rbis selected from the group consisting of -OH, oxo, -S(O)2CH3,,ny-273454135Docket No.: 79275-20025.40

[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, Rbis oxo.

[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, Rbis 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, Rbis C1-3alkyl 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, Rbis selected from the group consisting of,

[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, Rbis -C(O)-NH(C1-6alkyl).In some embodiments, - - . some .

[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, Rbis -C(O)-C1-6alkyl. In some embodiments, Rbis -C(O)-C1-3alkyl. In some embodiments, Rbis.

[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 Rbis -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, Rbis -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, Rbis -S(O)2-Ra, Rais methyl. In some embodiments, Rbis -S(O)2CH3.ny-273454136Docket No.: 79275-20025.40

[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, 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, deuterium, or halo. 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, deuterium, or halo. In some embodiments, Rbis selected from the group consisting,

[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, Rbis 3-10 membered heterocyclyl. In some embodiments, Rbis 3-6 membered heterocyclyl. In some embodiments, Rb

[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, 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.

[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, 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 with R4, and the atoms to which they are attached, to form a 5-6 membered heteroaryl optionally substituted with one or more Rc.

[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, Rcis independently at each occurrence, selected from the group consisting of halo, C1-6alkyl, -C(O)-C1-6alkyl, -C(O)-NH2, -ny-273454137Docket No.: 79275-20025.40 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 -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more –OH, or C1-6alkyl, 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 -S(O)2-C1-3alkyl, the C3-6cycloalkyl of Rcis optionally substituted with one or more –OH, or C1-3alkyl, 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, isopropyl,

[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, Rcis C1-6alkyl, -S(O)2-Ra. In some embodiments, Rcis C1-3alkyl. In some embodiments, Rcis methyl. In some embodiments, Rcis isopropyl.

[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, Rcis C1-6alkyl optionally substituted with one or more -S(O)2-Ra, wherein Rais C1-6alkyl. In some embodiments, Rcis C1-3alkyl optionally substituted with one or more -S(O)2-Ra, wherein Rais C1-3alkyl. In some embodiments, Rcis C1-3alkyl optionally substituted with one or more -S(O)2-Ra, wherein Rais methyl.

[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, Rcis C3-10cycloalkyl optionally substituted with one or more -OH, or C1-6alkyl. In some embodiments, Rcis C3-6cycloalkyl optionally substituted with one or more -OH, or C1-3alkyl. In some embodiments, Rcis selected from the group consistingny-273454138Docket No.: 79275-20025.40

[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, Rcis 3-10 membered heterocyclyl 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 3-6 membered heterocyclyl 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

[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, R5is H.

[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, R5is halo. In some embodiments, R5is Cl, or F.

[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, R5is -CN.

[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, 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, 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 independently selected from the group consisting of methyl,, and

[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, R5is 3-10 membered heterocyclyl. In some embodiments, R5is 3-6 membered heterocyclyl. In some embodiments, R5ny-273454139Docket No.: 79275-20025.40

[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, R5is C1-6alkoxy optionally substituted with one or more halo. In some embodiments, R5is C1-3alkoxy optionally substituted with one or more halo. In some embodiments, R5is C1-3alkoxy optionally substituted with one or more fluoro. In some embodiments, R5is .

[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, R6and R7are each independently H or 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.

[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, 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 embodiments, the bi-substitutedny-273454140Docket No.: 79275-20025.40

[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, 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 embodiments, the tri-ny-273454141Docket No.: 79275-20025.40

[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, 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 embodiments, the tetra-ny-273454142Docket No.: 79275-20025.40

[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, 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 embodiments, the bi-substituted

[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, 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 embodiments, the tri- substituted pyridine is selected from the group consisting

[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, 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 embodiments, the bi-substitutedny-273454143Docket No.: 79275-20025.40 pyrimidine is selected from the group consisting,

[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, L1, L2, and the ring bearingny-273454144Docket No.: 79275-20025.40 L3, R4, R6, and R7together form a heterocycle selected from the group consisting of. In some embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7ny-273454145Docket No.: 79275-20025.40 together form a heterocycle selected from the group consisting

[0120] 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 heteroaryl selected from the group consisting ofsome embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7selected from the group consisting ofandsome embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heteroaryl selected from the group consisting ofsome embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7ny-273454146Docket No.: 79275-20025.40 together form a heteroaryl selected from the group consisting of.

[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, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heterocycle selected from the group consisting ofsome embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heterocycleand the ring bearing L3, R4, R6, and R7together form a heterocycle selected from the groupny-273454147Docket No.: 79275-20025.40

[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, L1, L2, and the ring bearingny-273454148Docket No.: 79275-20025.40

[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, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heterocycle selected from the group consisting ofny-273454149Docket No.: 79275-20025.40some embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heterocycle selected from the group consisting,ring bearing L3, R4, R6, and R7together form a heterocycle selected from the group consisting ofDocket No.: 79275-20025.40embodiments, L1, L2, and the ring bearing L3, R4, R6, and R7together form. In some variations, L1, L2, and the ring bearing L3, R4, R6, and R7together form a heterocycle selected from the group consistingvariations, L1, L2, and the ring bearing L3, R4, R6, and R7together form. In certain variations, L1, L2, and the ring bearing L3, R4, R6, and R7together form.

[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, L1, L2, and the ring bearing L3, and R4together form a heterocycle selected from the group consistingny-273454151Docket No.: 79275-20025.40certain variations, L1, L2, and the ring bearing L3, and R4togethercertain variations, L1, L2, and the ring bearing L3, and R4together form

[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 bearingny-273454152Docket No.: 79275-20025.40ring bearing R6, and R7together form

[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 R6, and R7together form a heteroaryl selected from the group consisting of s1 2ome embodiments, L , L , and the ring bearing R6, and R7together formembodiments, L1, L2, and the ring bearing R6, and R7together.

[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, 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.

[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, n is 1, p is 0, L2is O and each of X1and X2is C(R5), wherein each R5is independently H, halo, -CN, 3-10 memberedny-273454153Docket No.: 79275-20025.40 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.

[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, 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.

[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, n is 1, L2is O, and each of X1and X2is N.

[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, 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.ny-273454154Docket No.: 79275-20025.40

[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, 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.

[0133] 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.

[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, m is an integer from 0 to 2; n is an integer from 1 to 2;ny-273454155Docket No.: 79275-20025.40 p is an integer from 0 to 1; R1, if present is, independently at each occurrence selected from the group consisting of halo, - CN, C1-3alkoxy, and C1-3alkyl, wherein the C1-3alkoxy of R1is optionally substituted with one or more halo, and the C1-3alkyl of R1is optionally substituted with one or more halo; R2is H, C1-3alkyl, C3-6cycloalkyl, or 3-6 membered heterocyclyl, wherein the C1-6alkyl 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; R3, if present, is C1-3alkyl; L1is C1-3alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium or C1-3alkyl, and wherein the C1-3alkyl is further optionally substituted with one or more -OH or C1-3alkoxy; L2is O; and either (1) L3is absent or is O, C3-6cycloalkyl, 3-6 membered heterocyclyl, or C1-3alkylene, wherein the C3-6cycloalkyl of L3is optionally substituted with one or more -OH or C1-3alkyl, 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, and the 3-6 membered heterocyclyl of L3is optionally substituted with one or more -OH or C1-3alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl of R4is optionally substituted with one or more C1-3alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-3alkyl, or -S(O)2-Ra, wherein the C1-3alkyl of Rdis optionally substituted with one or more -OH, (iv) -NS(O)-(C1-3alkyl)2, wherein the C1-3alkyl is optionally substituted with one or more – OH,ny-273454156Docket No.: 79275-20025.40 (v) -C(O)-N(Re)2wherein Reis independently at each occurrence H, C1-3alkyl, or 3-6 membered heterocycle, wherein the 3-6 membered heterocycle 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 3-6 membered heterocyclyl, wherein the 3-6 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, (vi) 3-6 membered heterocyclyl optionally substituted with one or more C1-3alkyl, -OH, oxo or -S(O)2Ra, (vii) -S(O)-N(C1-3alkyl)-(C1-3alkyl), (viii) -CN, (ix) -(CH2)qOH, wherein q is an integer from 0-3, (x) -C(O)-C1-3alkyl, or (xi) -P(O)(C1-3alkyl)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 5-8 membered heterocyclyl or a 5-10 membered heteroaryl, wherein the 5-8 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, C1-3alkyl, -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, and 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, and whereinny-273454157Docket No.: 79275-20025.40 the C1-3alkyl of the C3-6cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-10 membered heteroaryl is optionally substituted with one or more Rc, wherein 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 or C1-3alkyl, and the 3-6 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-3alkyl, and wherein the C1-3alkyl of the 3-6 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-3alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-3alkyl, or -N(C1-3alkyl)-C(O)-C1-3alkyl, (ii) 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, or -C(O)-C3-6heterocyclyl, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH, (iii) 3-6 membered heterocyclyl optionally substituted with one or more C1-3alkyl, or (iv) NH(C1-3alkyl); 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 the C1-3alkoxy 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.

[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,ny-273454158Docket No.: 79275-20025.40 m is an integer from 0 to 2; n is 1; p is an integer from 0; R1, if present is, independently at each occurrence selected from the group consisting of halo, - CN, C1-3alkoxy, and C1-3alkyl, wherein the C1-3alkoxy of R1is optionally substituted with one or more halo, and the C1-3alkyl of R1is optionally substituted with one or more halo; R2is H, C1-3alkyl, C3-6cycloalkyl, or 3-6 membered heterocyclyl, wherein the C1-6alkyl 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; L1is C1-3alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium; L2is O; and either (1) L3is absent or is O, C3-6cycloalkyl, 3-6 membered heterocyclyl, or C1-3alkylene, wherein the C3-6cycloalkyl of L3is optionally substituted with one or more -OH or C1-3alkyl, 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, and the 3-6 membered heterocyclyl of L3is optionally substituted with one or more -OH or C1-3alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl of R4is optionally substituted with one or more C1-3alkyl; (iii) -N(Rd)2, wherein Rdis independently at each occurrence H, C1-3alkyl, or -S(O)2-Ra, wherein the C1-3alkyl of Rdis optionally substituted with one or more -OH, (iv) -NS(O)-(C1-3alkyl)2, wherein the C1-3alkyl is optionally substituted with one or more – OH,ny-273454159Docket No.: 79275-20025.40 (v) -C(O)-N(Re)2wherein Reis independently at each occurrence H, C1-3alkyl, or 3-6 membered heterocycle, wherein the 3-6 membered heterocycle 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 3-6 membered heterocyclyl, wherein the 3-6 membered heterocyclyl is optionally substituted with one or more halo, oxo, -OH, NH2, -NH-S(O)2-Ra, or -S(O)2-Ra, (vi) 3-6 membered heterocyclyl optionally substituted with one or more C1-3alkyl, -OH, oxo or -S(O)2Ra, (ix) -(CH2)qOH, wherein q is an integer from 0-3; 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 5-8 membered heterocyclyl or a 5-10 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, C1-3alkyl, -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, and 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, and wherein the C1-3alkyl of the C3-6cycloalkyl of Rbis further optionally substituted with one or more -OH, deuterium, or halo, and the 5-10 membered heteroaryl is optionally substituted with one or more Rc, whereinny-273454160Docket No.: 79275-20025.40 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 or C1-3alkyl, and the 3-6 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-3alkyl, and wherein the C1-3alkyl of the 3-6 membered heterocyclyl of Rcis further optionally substituted with one or more -OH; Rais, independently at each occurrence: (i) C1-3alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-3alkyl, or -N(C1-3alkyl)-C(O)-C1-3alkyl, (ii) 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, or -C(O)-C3-6heterocyclyl, or C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more -OH, (iii) 3-6 membered heterocyclyl optionally substituted with one or more C1-3alkyl, or (iv) NH(C1-3alkyl); 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 the C1-3alkoxy 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.

[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, m is an integer from 0 to 2; n is 1; p is an integer from 0;ny-273454161Docket No.: 79275-20025.40 R1, if present is, independently at each occurrence selected from the group consisting of halo, - CN, C1-3alkoxy, and C1-3alkyl, wherein the C1-3alkoxy of R1is optionally substituted with one or more halo, and the C1-3alkyl of R1is optionally substituted with one or more halo; R2is H; L1is C1-3alkylene, wherein the C1-6alkylene of L1is optionally substituted with one or more deuterium; L2is O; and either (1) L3is absent or is C1-3alkylene, wherein the C1-3alkylene of L3is optionally substituted with one or more -OH or C1-3alkyl; X1and X2are each independently N or C(R5); and R4is: (i) -S(O)2-Ra; (ii) -(CH2)qOH, wherein q is an integer from 0-3; 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 5-8 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 oxo, or C3-6cycloalkyl, wherein the C3-6cycloalkyl is optionally substituted with one or more -OH, C3-6cycloalkyl, or C1-3alkyl, and the 5-10 membered heteroaryl is optionally substituted with one or more Rc, wherein Rcis, independently at each occurrence, selected from the group consisting of C1-3alkyl, C3-6cycloalkyl, wherein the C3-6cycloalkyl of Rcis optionally substituted with one or more -OH or C1-3alkyl; Rais, independently at each occurrence: (i) C1-3alkyl optionally substituted with one or more halo, -OH, -S(O)2-C1-3alkyl, or -N(C1-3alkyl)-C(O)-C1-3alkyl; R5is, independently at each occurrence, H, halo, C1-3alkyl, or C1-3alkoxy, wherein the C1-3alkyl of R5is optionally substituted with one or more halo or -OH, andny-273454162Docket No.: 79275-20025.40 the C1-3alkoxy 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.

[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, the compound is a compound of formulastereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: n is 1 or 2; and R1, R2, R3, L1, L3, R4, X1, X2, R6, and R7are as defined for formula (I). In some embodiments, the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is a compound of formulany-273454163Docket No.: 79275-20025.40stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, n, p, R1, R2, R3, R4, R5, R6, R7, L1, L3, X1, X2, and Raare as defined for formula (I).

[0138] In some embodiments of a compound of formula (I), the compound is a compound ofstereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, p, R1, R2, R3, R4, R5, R6, and R7, L1, L3, are as defined for formula (I). In some embodiments, the compound of formulany-273454164Docket No.: 79275-20025.40stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, R1, R2, R4, R5, R6, R7, L1, and L3, are as defined for formula (I). In some embodiments of a compound of formula (I), the compound is a compound of formula (I-stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, p, R1, R2, R3, L1, L3, R4, and R5are as defined for formula (I). In some embodiments the compound of formula (I-C) is astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, p, R1, R2, R3, R4, R5, L1, and L3, and are as defined for formula (I).ny-273454165Docket No.: 79275-20025.40

[0139] In some embodiments of a compound of formula (I), the compound is a compound ofstereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m, p, R1, R2, R3, L1, L3, and R4, are as defined for formula (I).

[0140] In some embodiments of a compound of formula (I), the compound is a compound of formulastereoisomer 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;1 2 3 1 2 b c 6 7R , R , R L , X , R , R , R , and R of formula (I-E) are as defined for a compound of formula (I).

[0141] In some embodiments the compound is a compound of formula (I-E) is a compound of formulastereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: ring A is 5-10 memberedny-273454166Docket No.: 79275-20025.40 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;1 2 3 1 1 b c 6 7R , R , R , L , X , R , R , R , and R of formula (I).

[0142] In some embodiments, the compound of formula (I-E) is a compound of formulastereoisomer 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, and Rbare as defined for formula (I); and wherein the dashed line represents a single or double bond. In some embodiments, the moiety representedhas a stereochemical configuration representedny-273454167Docket No.: 79275-20025.40

[0143] In some embodiments, the compound of formula (I-E) is a compound of formulastereoisomer 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, and Rcare as defined for formula (I); and wherein the dashed line represents a single or double bond. In some embodiments of a compound of (I-E5), the moiety representeda stereochemical configuration representedsome embodiments theny-273454168Docket No.: 79275-20025.40

[0144] In some embodiments of a compound of formula (I), the compound is a compound of formulastereoisomer 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, and Rcof formula (I-F) are as defined for a compound of formula (I). In some embodiments, the compound of formula (I-F) is a compound of formula(I-F1), orstereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0145] In some embodiments of a compound of formula (I), such as a compound of formula (I- E), or (I-F), 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 heterocyclylny-273454169Docket No.: 79275-20025.40 is optionally substituted with one or more of Rb. In some embodiments, ring A is selected fromof attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0146] In some embodiments of a compound of formula (I-E), or (I-F), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heteroaryl optionally substituted with one or more Rc. In some embodiments, ring A is a 5-6 membered heteroaryl optionally substituted with one or more Rc. In some embodiments, ring A is selected from the group consisting ofny-273454170Docket No.: 79275-20025.40,wherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0147] In some embodiments, the compound of formula (I), is a compound of formula(I-G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, 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, and Rcof formula (I-G) are as defined for a compound of formula (I). 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. In some embodiments, ring A is selected from the group consistingny-273454171Docket No.: 79275-20025.40wherein wherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond. In some embodiments, ring A is a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with one or more Rc. In some embodiments ring A is selected from the group consisting ofny-273454172Docket No.: 79275-20025.40wherein ## represent a point of attachment to the remainder of the molecule and the dashed line represents a single or double bond.

[0148] In some embodiments of a compound of formula (I), the compound is a compound ofstereoisomer 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;1 2 3 1 b c 2 3 4R , R , R , L , R , R , X , X , and X are as defined for formula (I). In some embodiments the compound of formula (I-H), is a compound of formula(I-H2), 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, R7, L1, Rb, and Rcare as defined for formula (I).ny-273454173Docket No.: 79275-20025.40

[0149] It is to be understood that any variation or embodiment of m, n, p, R1, R2, R3, L1, L2L3, X1, X2, X3, X4, R4, R5, R6, R7, 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, X1, X2, X3, X4, R4, R5, R6, R7, 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 C1-6alkyl, R4is SO2Rawherein Rais C1-6alkyl, X1is N, X2is N, R6is H, and R7is H, can be combined to give.

[0150] In some embodiments of 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 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.ny-273454174Docket No.: 79275-20025.40ny-273454175Docket No.: 79275-20025.40ny-273454176Docket No.: 79275-20025.40ny-273454177Docket No.: 79275-20025.40 # 29 3031 32ny-273454178Docket No.: 79275-20025.40 # 37 38 3940ny-273454179Docket No.: 79275-20025.40Structure / Nameny-273454180Docket No.: 79275-20025.40 # Structure / Name 53 5-chloro-1'-{2-[(1-methanesulfonyl- 1,2,3,4-tetrahydroquinolin-6- yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one 54 5-chloro-1'-{2-[(2-methanesulfonyl-2,3- dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one 551'-{2-[(2-methanesulfonyl-1,2,3,4- tetrahydroisoquinolin-6-yl)oxy]ethyl}-1- methyl-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one 56 1'-{2-[(1-acetyl-1,2,3,4- tetrahydroquinolin-6-yl)oxy]ethyl}-5- chloro-1,2-dihydrospiro[indole-3,4'- piperidin]-2-oneny-273454181Docket No.: 79275-20025.40ny-273454182Docket No.: 79275-20025.40 # 69 7071 72ny-273454183Docket No.: 79275-20025.40ny-273454184Docket No.: 79275-20025.40 # 85 86 87 88ny-273454185Docket No.: 79275-20025.40 # 93 9495 96ny-273454186Docket No.: 79275-20025.40 # 101 102103104ny-273454187Docket No.: 79275-20025.40 # Structure / Name # Structure / Name 109 1'-{2-[4-(3-methanesulfonyloxetan-3- yl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile 110 5-chloro-1'-[2-(4-methanesulfonyl-3- methylphenoxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one111 1'-[2-(4-methanesulfonyl-3- methylphenoxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile 1125-chloro-1'-[2-(4- difluoromethanesulfonylphenoxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2- oneny-273454188Docket No.: 79275-20025.40 # 117ny-273454189Docket No.: 79275-20025.40ny-273454190Docket No.: 79275-20025.40 # 133 134 135 136ny-273454191Docket No.: 79275-20025.40 # 141142 143 144ny-273454192Docket No.: 79275-20025.40 # 149150151152ny-273454193Docket No.: 79275-20025.40 # Structure / Name # Structure / Name 157 1'-{2-[4-(1-cyano-1- methylethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile 158 5-chloro-1'-[2-({6-[(3-methyloxetan-3- yl)sulfonyl]pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one 1591-(2-hydroxyethyl)-1'-{2-[4- methanesulfonyl-3- (trifluoromethyl)phenoxy]ethyl}-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]- 5-carbonitrile 160 5-chloro-1-(2-hydroxyethyl)-1'-{2-[4-(3- methanesulfonyloxetan-3- yl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-oneny-273454194Docket No.: 79275-20025.40 # 165d 1661 3 167168ny-273454195Docket No.: 79275-20025.40 # 173 174175 176ny-273454196Docket No.: 79275-20025.40ny-273454197Docket No.: 79275-20025.40 #Structure / Name 189190 191 192ny-273454198Docket No.: 79275-20025.40ny-273454199Docket No.: 79275-20025.40ny-2734541100Docket No.: 79275-20025.40 # 213 214215 216ny-2734541101Docket No.: 79275-20025.40 # 221 222223 224ny-2734541102Docket No.: 79275-20025.40 # Structure / Name # Structure / Name 229 4-(2-{5-chloro-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)-2-fluoro-N-methylbenzamide 2304-(2-{5-chloro-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)-2-fluoro-N,N- dimethylbenzamideny-2734541103Docket No.: 79275-20025.40ny-2734541104Docket No.: 79275-20025.40 # 245246247 248ny-2734541105Docket No.: 79275-20025.40 # 253254255 256ny-2734541106Docket No.: 79275-20025.40 #Structure / Name 2611 262 263264ny-2734541107Docket No.: 79275-20025.40 # Structure / Name # Structure / Name 2695-chloro-1'-(2-{4-[(cis) or (trans)-3- hydroxy-1- methanesulfonylcyclobutyl]phenoxy}ethy l)-1,2-dihydrospiro[indole-3,4'-piperidin]- 2-one 2705-chloro-1'-(2-{4-[(trans) or (cis)-3- hydroxy-1- methanesulfonylcyclobutyl]phenoxy}ethy l)-1,2-dihydrospiro[indole-3,4'-piperidin]- 2-oneny-2734541108Docket No.: 79275-20025.40ny-2734541109Docket No.: 79275-20025.40 # 285286287288ny-2734541110Docket No.: 79275-20025.40 # 293 294 295 296ny-2734541111Docket No.: 79275-20025.40 #Structure / Name 301 302303 304ny-2734541112Docket No.: 79275-20025.40Structure / Nameny-2734541113Docket No.: 79275-20025.40ny-2734541114Docket No.: 79275-20025.40ny-2734541115Docket No.: 79275-20025.40ny-2734541116Docket No.: 79275-20025.40 #Structure / Name 342343 344 345ny-2734541117Docket No.: 79275-20025.40 # 350 351 352 353ny-2734541118Docket No.: 79275-20025.40ny-2734541119Docket No.: 79275-20025.40 # 366 367368369ny-2734541120Docket No.: 79275-20025.40ny-2734541121Docket No.: 79275-20025.40 # 382383384385ny-2734541122Docket No.: 79275-20025.40 # 390 391 392 393ny-2734541123Docket No.: 79275-20025.40 # 398 399 400 401ny-2734541124Docket No.: 79275-20025.40ny-2734541125Docket No.: 79275-20025.40ny-2734541126Docket No.: 79275-20025.40ny-2734541127Docket No.: 79275-20025.40 # 430 4311 432 1 4331ny-2734541128Docket No.: 79275-20025.40 # Structure / Name # Structure / Name 4381'-(2-{[1-(3-hydroxy-3- methylcyclobutyl)-1H-pyrazolo[3,4- b]pyridin-5-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile 4395-(2-{5-chloro-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)-1-[(cis)-3-hydroxy-3- methylcyclobutyl]-1H-1,3-benzodiazole- 7-carbonitrile 440 5-chloro-1'-[2-({3-[(cis)-3-hydroxy-3- methylcyclobutyl]-3H-[1,2,3]triazolo[4,5- b]pyridin-6-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one 441 5-chloro-1'-(2-{[2-(2,2-dimethyl-1,3- dioxolan-4-yl)pyrimidin-5-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2- oneny-2734541129Docket No.: 79275-20025.40 # Structure / Name # Structure / Name 4461'-(2-{[7-(difluoromethyl)-1-[(cis)-3- hydroxy-3-methylcyclobutyl]-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile 447 5-chloro-1'-(2-{[7-(difluoromethoxy)-1- [(cis)-3-hydroxy-3-methylcyclobutyl]- 1H-1,3-benzodiazol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one 4481'-(2-{[7-(difluoromethoxy)-1-[(cis)-3- hydroxy-3-methylcyclobutyl]-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile 449 5-chloro-1'-(2-{[2-(2-hydroxypropan-2- yl)pyrimidin-5-yl]oxy}ethyl)-7-iodo-1,2- dihydrospiro[indole-3,4'-piperidin]-2-oneny-2734541130Docket No.: 79275-20025.40 # 454 455456457ny-2734541131Docket No.: 79275-20025.40ny-2734541132Docket No.: 79275-20025.40 # Structure / Name H N O Cl N CF NOHO N 4472N ydroxy-3- 5-chloro-1'-(2-{3-[(cis)-3-hydroxy-3- methyl)- methylcyclobutyl]-4-(trifluoromethyl)- azol-5- 3H-1,3,5-triazainden-6- o[indole- yloxy}ethyl)spiro[indoline-3,4'- itrile piperidin]-2-oneN CF OH O N N 471N 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3- methylcyclobutyl]-7-(trifluoromethyl)- 1H-imidazo[4,5-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one

[0151] In some embodiments, a compound of formula (I) is selected from the group consisting of: 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2-methoxyethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-bromo-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile; 1'-{2-[(1-methyl-1H-indazol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-bromo-1-(2-hydroxyethyl)-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2-methoxyethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2-methoxyethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile;ny-2734541133Docket No.: 79275-20025.40 1'-{2-[(2-methanesulfonyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-1-methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-1-methyl-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1-[2-(4-methanesulfonylphenoxy)ethyl]-1',2'-dihydrospiro[azepane-4,3'-indol]-2'-one; 1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)propyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-1H-indazol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 1'-[2-(4-difluoromethanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(3,5-difluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 1-(3-hydroxycyclobutyl)-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[4-(3-methanesulfonylpropanesulfonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(cyclopropanesulfonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5,7-dichloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 1-methyl-1'-{2-[4-(2-oxopyrrolidin-1-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]- 2-one; 1'-{2-[(1-acetyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1-methyl-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1-methyl-1'-{2-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1-methyl-1'-[2-(quinoxalin-6-yloxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1-methyl-1'-{2-[(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-(2-{1-methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,3-dihydro- 1lambda6-benzothiophene-1,1-dione;ny-2734541134Docket No.: 79275-20025.40 5-chloro-1-(2-hydroxyethyl)-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(oxetan-3-yl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 7-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[1-(propan-2-yl)-1H-indazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-methanesulfonylpropyl)-1H-indazol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(6-methanesulfonylpyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[(2-methanesulfonyl-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2-dihydrospiro[indole-3,4'-piperidin]- 2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)propyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 5-chloro-1'-{2-[4-(3-methanesulfonylpropanesulfonyl)phenoxy]ethyl}-1-methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1-methyl-1'-{2-[4-(1-methyl-1H-pyrazol-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1-methyl-1'-{2-[(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541135Docket No.: 79275-20025.40 1-methyl-1'-{2-[(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(3-fluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-7-carbonitrile; 5-chloro-1'-(2-{4-[(3-hydroxycyclobutyl)sulfonyl]phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[1-(oxetan-3-yl)-1H-indazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[4-(2-hydroxyethanesulfonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{1-[(1-methyl-1H-indazol-5-yl)oxy]propan-2-yl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-5-methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(quinoxalin-6-yloxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[2-(3,5-difluoro-4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(3-methyl-1H-pyrazol-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-(3,5-difluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(1-methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(1-acetyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-5-chloro-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one;ny-2734541136Docket No.: 79275-20025.40 5-chloro-1'-[2-(1H-indazol-5-yloxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-1,2,3,4- tetrahydroquinoline-1-carboxamide; 1'-{2-[(2-acetyl-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-5-chloro-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonyl-3-methylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-(4-difluoromethanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-difluoromethanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]- 5-carbonitrile; N-{2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)benzenesulfonyl]ethyl}-N-methylacetamide; 5-chloro-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-methanesulfonyl-3-methylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(2-methanesulfonyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{4-[(3-methyloxetan-3-yl)sulfonyl]phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-1,2,3,4- tetrahydroisoquinoline-2-carboxamide; 5-chloro-1'-(2-{[1-(3-hydroxycyclobutyl)-1H-indazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,3-dihydro- 1lambda6-benzothiophene-1,1-dione; 1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-5-chloro-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one;ny-2734541137Docket No.: 79275-20025.40 5-chloro-1'-(2-{4-[(3-hydroxycyclobutyl)sulfonyl]phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxycyclobutyl)-1H-indazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-2,3- dihydro-1H-isoindole-2-carboxamide; 1'-(2-{4-[(3-methyloxetan-3-yl)sulfonyl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-(2-fluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 2-oxo-1'-(2-{[2-oxo-1-(propan-2-yl)-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(1-methanesulfonylcyclopropyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-oxo-1-(propan-2-yl)-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{1-[3-(difluoromethyl)-4-methanesulfonylphenoxy]propan-2-yl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylcyclopropyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{1-[3-(difluoromethyl)-4-methanesulfonylphenoxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile;ny-2734541138Docket No.: 79275-20025.40 5-chloro-1-(3-hydroxycyclobutyl)-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N- methylmethanesulfonamide; N-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N- methylmethanesulfonamide; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- methanesulfonylbenzonitrile; 5-chloro-1'-(2-{[1-(2,2-difluoroethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-methanesulfonyl-3-(trifluoromethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-methanesulfonyl-3-(trifluoromethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; methyl 1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)benzenesulfonyl]cyclopropane-1-carboxylate; 1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-1-(2-hydroxyethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-1-(2-hydroxyethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[1-(2,2-difluoroethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1-(3-hydroxycyclobutyl)-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-{2-[(1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)benzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzamide;ny-2734541139Docket No.: 79275-20025.40 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)pyridine-2- carboxamide; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-1-methyl-3,4- dihydro-1H-2lambda6,1-benzothiazine-2,2-dione; N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)phenyl]methanesulfonamide; 1'-{2-[(1-methyl-2,2-dioxo-3,4-dihydro-1H-2lambda6,1-benzothiazin-6-yl)oxy]ethyl}-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(oxetan-3-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(3-hydroxycyclobutyl)-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1-(3-hydroxycyclobutyl)-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(3-hydroxycyclobutyl)-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-{[1-(hydroxymethyl)cyclopropyl]sulfonyl}phenoxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(3-fluoro-4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[(1-acetyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(8-methyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(8-methyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-[2-(4-methanesulfonyl-3,5-dimethylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541140Docket No.: 79275-20025.40 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 6-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-1,2,3,4- tetrahydroisoquinoline-2-carboxamide; 5-chloro-1'-(2-{[1-(3-hydroxycyclobutyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonyl-3,5-dimethylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-(1-cyano-1-methylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]- 5-carbonitrile; 2-oxo-1'-(2-{[2-oxo-1-(propan-2-yl)-2,3-dihydro-1H-indol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(6-methanesulfonyl-5-methylpyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile;ny-2734541141Docket No.: 79275-20025.40 5-chloro-1'-[2-({3-methyl-2-oxo-1H,2H,3H-imidazo[4,5-b]pyridin-6-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(6-methanesulfonyl-5-methylpyridin-3-yl)oxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[(8-acetyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-5-chloro-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(8-acetyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-methanesulfonyl-3-(oxetan-3-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-(3-chloro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(3-chloro-4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-oxo-1-(propan-2-yl)-2,3-dihydro-1H-indol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-[1-(3,5-difluoro-4-methanesulfonylphenoxy)propan-2-yl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile;ny-2734541142Docket No.: 79275-20025.40 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-methylbenzamide; 5-chloro-1'-{2-[(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluoro-N,N- dimethylbenzamide; 5-chloro-1'-{2-[3-fluoro-4-(morpholine-4-carbonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 4-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzoyl]- 1lambda6-thiomorpholine-1,1-dione; 1'-[2-(4-{[1-(azetidine-1-carbonyl)cyclopropyl]sulfonyl}phenoxy)ethyl]-5-chloro-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-fluoro-4-(3-methanesulfonylazetidine-1-carbonyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-methyl-3,4- dihydro-2H-1lambda6,2-benzothiazine-1,1-dione; 1'-{2-[(2-methyl-1,1-dioxo-3,4-dihydro-2H-1lambda6,2-benzothiazin-6-yl)oxy]ethyl}-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(azetidine-1-carbonyl)-3-fluorophenoxy]ethyl}-5-chloro-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[3,5-difluoro-4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-fluoro-4-(3-hydroxyazetidine-1-carbonyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile;ny-2734541143Docket No.: 79275-20025.40 N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,6- difluorophenyl]-N-methylmethanesulfonamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluoro-N- methylbenzamide; 1-(2-hydroxyethyl)-1'-{2-[4-methanesulfonyl-3-(trifluoromethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; N-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,6- difluorophenyl]-N-methylmethanesulfonamide; 1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)benzenesulfonyl]- N-methylcyclopropane-1-carboxamide; 5-chloro-1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)benzenesulfonyl]- N,N-dimethylcyclopropane-1-carboxamide; 1'-{2-[3,5-difluoro-4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[3-(1,2-dihydroxyethyl)-4-methanesulfonylphenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N,N- dimethylpyridine-2-carboxamide; 4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzamide; 1'-{2-[4-(3-aminoazetidine-1-carbonyl)-3-fluorophenoxy]ethyl}-5-chloro-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(3-methyloxetan-3-yl)sulfonyl]pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one;ny-2734541144Docket No.: 79275-20025.40 5-chloro-1'-(2-{[1-(3-hydroxycyclobutyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; N-{1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- fluorobenzoyl]azetidin-3-yl}methanesulfonamide; 1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methylbenzamide; 1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(2-hydroxyethyl)-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-[2-(4-{[dimethyl(oxo)-lambda6-sulfanylidene]amino}phenoxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-(2,2,2-trifluoroethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-(1-methanesulfonylcyclobutyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[3-(difluoromethoxy)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[3-(difluoromethoxy)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one;ny-2734541145Docket No.: 79275-20025.40 5-chloro-1'-{2-[(6-{[1-(hydroxymethyl)cyclopropyl]sulfonyl}pyridin-3-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{2-[(7-fluoro-1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(4-methanesulfonyloxan-4-yl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(4-methanesulfonyloxan-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-methyl-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{3-oxo-3H-spiro[2-benzofuran-1,3'-oxetan]-5-yloxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)-3-(trifluoromethyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; N-(4-{2-[5-chloro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl]ethoxy}-2-(trifluoromethyl)phenyl)methanesulfonamide; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)-3-(trifluoromethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-3,4-dihydro-2H- 1lambda6,2-benzothiazine-1,1-dione; 2-oxo-1'-{2-[(1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile;ny-2734541146Docket No.: 79275-20025.40 5-chloro-1'-{2-[(1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[(7-fluoro-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-{2-[(1,1-dioxo-3,4-dihydro-2H-1lambda6,2-benzothiazin-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({2-[(3-methyloxetan-3-yl)oxy]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 3-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N- methyloxetane-3-carboxamide; 3-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N,N- dimethyloxetane-3-carboxamide; 2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-1lambda6- thiolane-1,1-dione; 2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-1lambda6- thiolane-1,1-dione; 1'-[2-(4-{6-methanesulfonyl-2-oxaspiro[3.3]heptan-6-yl}phenoxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{4-[3-(azetidine-1-carbonyl)oxetan-3-yl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)pyrimidine-2- carboxamide; 2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-1lambda6- thiolane-1,1-dione; 1'-(2-{4-[3-(ethanesulfonyl)oxetan-3-yl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 2-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-2- methylpropanamide; 1'-{2-[4-(1,1-dioxo-1lambda6-thiolan-2-yl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- (difluoromethyl)benzamide;ny-2734541147Docket No.: 79275-20025.40 1'-{2-[3,5-difluoro-4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-methyl-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-[2-({2-[(3-methyloxetan-3-yl)oxy]pyrimidin-5-yl}oxy)ethyl]-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-(2-{4-[3-(3-fluoroazetidine-1-carbonyl)oxetan-3-yl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- (difluoromethyl)benzamide; 5-chloro-1'-[2-(4-{6-methanesulfonyl-2-oxaspiro[3.3]heptan-6-yl}phenoxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylethyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N-(2- hydroxyethyl)methanesulfonamide; 6-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzoyl]- 2lambda6-thia-6-azaspiro[3.3]heptane-2,2-dione; 5-chloro-1'-[2-(3-fluoro-4-{6-methanesulfonyl-2,6-diazaspiro[3.3]heptane-2- carbonyl}phenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 4-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,6- difluorobenzoyl]-1lambda6-thiomorpholine-1,1-dione; 5-chloro-1'-(2-{[8-(2-hydroxyethyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-(1,1-dioxo-1lambda6-thiomorpholine-4-carbonyl)-3,5-difluorophenoxy]ethyl}-1- methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 4-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- (trifluoromethyl)benzoyl]-1lambda6-thiomorpholine-1,1-dione; 1'-{2-[4-(1,1-dioxo-1lambda6-thiomorpholine-4-carbonyl)-3-(trifluoromethyl)phenoxy]ethyl}-1- methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[6-(2-methanesulfonylpropan-2-yl)pyridin-3-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile;ny-2734541148Docket No.: 79275-20025.40 5-chloro-1'-{2-[4-(3-hydroxy-1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(4-{2-[5-chloro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl]ethoxy}-2-(trifluoromethyl)benzoyl)-1lambda6-thiomorpholine-1,1-dione; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-(1,1-dioxo- 1lambda6-thiolan-3-yl)-2-fluorobenzamide; 5-chloro-1'-{2-[4-(3-hydroxy-1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(3-hydroxy-1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-(1,1-dioxo- 1lambda6-thian-4-yl)-2-fluorobenzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-(1,1-dioxo- 1lambda6-thiolan-3-yl)-2-fluorobenzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-(1,1-dioxo- 1lambda6-thiolan-3-yl)-2-fluorobenzamide; 5-chloro-1'-(2-{[8-(3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethoxy)-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylethyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylethyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541149Docket No.: 79275-20025.40 5-chloro-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H,4H-pyrido[2,3-d][1,3]oxazin- 6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-ethyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-cyclopropyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-cyclopropyl-3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylazetidin-1-yl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-{2-[(7-oxo-8-{[3-hydroxy-3-methylcyclobutyl]methyl}-5,6,7,8-tetrahydro- 1,8-naphthyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(7-oxo-8-{[3-hydroxy-3-methylcyclobutyl]methyl}-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxyazetidin-1-yl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({8-[3-(hydroxymethyl)cyclobutyl]-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({7-oxo-8-[3-hydroxy-3-(propan-2-yl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-ethyl-3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ;ny-2734541150Docket No.: 79275-20025.40 5-(difluoromethyl)-1'-[2-({8-[(3-hydroxy-3-methylcyclobutyl)methyl]-7-oxo-5,6,7,8-tetrahydro- 1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-ethyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethoxy)-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[3-(hydroxymethyl)cyclobutyl]-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[(3-hydroxy-3-methylcyclobutyl)methyl]-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethoxy)-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-7-iodo-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-hydroxy-3-(propan-2-yl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[6-(1-hydroxyethyl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one ; 1'-(2-{[6-(1-hydroxyethyl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[5-(difluoromethyl)-7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro- 1,8-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[5-(difluoromethyl)-7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]- 7,8-dihydro-1,8-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5-(trifluoromethyl)-7,8-dihydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541151Docket No.: 79275-20025.40 5-(difluoromethyl)-1'-[2-({7-oxo-8-[3-hydroxy-3-methylcyclobutyl]-5-(trifluoromethyl)-7,8- dihydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3- b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3- b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({1-[3-hydroxy-3-methylcyclobutyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({1-[3-hydroxy-3-methylcyclobutyl]-1H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H-pyrido[2,3-d]pyrimidin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[3-hydroxy-3-methylcyclobutyl]-1H,2H,3H,4H-pyrido[2,3- d]pyrimidin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[3-hydroxy-3-methylcyclobutyl]-1H-pyrazolo[3,4-b]pyridin-5-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-oxo-4-[3-hydroxy-3-methylcyclobutyl]-3H,4H-pyrido[2,3-b]pyrazin-7- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[4-(3-hydroxy-3-methylcyclobutyl)pyrido[3,2-d]pyrimidin-7-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylazetidin-1-yl)pyrido[2,3-d]pyridazin-3-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[4-(3-hydroxy-3-methylazetidin-1-yl)pyrido[3,2-d]pyrimidin-7-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxyazetidin-1-yl)pyrido[2,3-d]pyridazin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541152Docket No.: 79275-20025.40 5-chloro-1'-(2-{[4-(3-hydroxyazetidin-1-yl)pyrido[3,2-d]pyrimidin-7-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-[3-hydroxy-3-methylcyclobutyl]-3H-imidazo[4,5-b]pyridin-6-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({2-oxo-3-[3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-imidazo[4,5-b]pyridin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[3-(hydroxymethyl)azetidin-1-yl]-1,7-naphthyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-2H,3H-[1,3]oxazolo[4,5- b]pyridin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-{6-hydroxy-2-azaspiro[3.3]heptan-2-yl}pyrimidin-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(3-ethyl-3-hydroxyazetidin-1-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-cyclopropyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[6-(1-hydroxyethyl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5,7-dichloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[6-(1-hydroxy-2-methanesulfonylpropan-2-yl)-5-(trifluoromethyl)pyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[6-(1-hydroxy-2-methanesulfonylpropan-2-yl)-5-(trifluoromethyl)pyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[6-(1-hydroxy-2-methanesulfonylpropan-2-yl)-5-(trifluoromethyl)pyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[6-(3-hydroxy-3-methylazetidin-1-yl)-5-(trifluoromethyl)pyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541153Docket No.: 79275-20025.40 1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-7,8-dihydro-1,8-naphthyridin-3-yl]oxy}ethyl)- 2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5,7-dichloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[6-(2-hydroxypropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(1-methanesulfonylpiperidin-4-yl)phenoxy]ethyl}-1-(2H3)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(2H3)methyl-1'-(2-{4-[methyl(methylimino)oxo-lambda6-sulfanyl]-3- (trifluoromethyl)phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(2H3)methyl-1'-(2-{4-[3-(propane-2-sulfonyl)oxetan-3-yl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1-(2H3)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(2H3)methyl-1'-{2-[(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(2-hydroxy-2-methylpropyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1-(2H3)methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2H3)methyl-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1-(2H3)methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[1-(hydroxymethyl)cyclopropyl]pyrimidin-5-yl}oxy)ethyl]-1-(2H3)methyl- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 6-{2-[5-chloro-1-(2H3)methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl]ethoxy}-8- fluoro-3,4-dihydro-2H-1lambda6,2-benzothiazine-1,1-dione;ny-2734541154Docket No.: 79275-20025.40 5-chloro-1'-(2-{[2-(3-methanesulfonyloxetan-3-yl)pyrimidin-5-yl]oxy}ethyl)-1-(2H3)methyl- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1-(2H3)methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1-(2H3)methyl- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylethyl)pyrimidin-5-yl]oxy}ethyl)-1-(2H3)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}(1,1,2,2-2H4)ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-2H-indazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-2H-indazol-5-yl]oxy}ethyl)-2- oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-(3-hydroxyoxetan-3-yl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-hydroxycyclobutyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-(2-{[6-(3-hydroxy-3-methylazetidin-1-yl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[2-(1-hydroxy-2-methylpropan-2-yl)pyrimidin-5-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,2,3-benzotriazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,2,3-benzotriazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile;ny-2734541155Docket No.: 79275-20025.40 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-1-(3-hydroxy-3- methylcyclobutyl)-1H-1,3-benzodiazole-7-carbonitrile; 5-chloro-1'-(2-{[3-(3-hydroxy-3-methylcyclobutyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-6- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(2,2-dimethyl-1,3-dioxolan-4-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-2-methyl-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-2-methyl-7-(trifluoromethyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(1-methanesulfonylpiperidin-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[7-(difluoromethyl)-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[7-(difluoromethyl)-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[7-(difluoromethoxy)-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[7-(difluoromethoxy)-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]oxy}ethyl)-7-iodo-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[3-(3-hydroxy-3-methylcyclobutyl)-2-methyl-3H-imidazo[4,5-b]pyridin-6- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(2-hydroxy-2-methylpropyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-7-iodo-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541156Docket No.: 79275-20025.40 5-chloro-1'-(2-{[7-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[7-fluoro-1-(3-hydroxy-3-methylcyclobutyl)-1H-1,3-benzodiazol-5-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-2-oxo-8-(trifluoromethyl)-1,2,3,4- tetrahydroquinazolin-6-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-2-oxo-8-(trifluoromethyl)-1,2,3,4- tetrahydroquinazolin-6-yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile; 5-chloro-1'-[2-({7,7-dimethyl-5-oxo-5H,7H-furo[3,4-b]pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-{6-hydroxy-6-methyl-2-azaspiro[3.3]heptan-2-yl}pyrimidin-5-yl)oxy]ethyl}- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[1'-(3-hydroxy-3-methylcyclobutyl)-2'-oxo-1',2'-dihydrospiro[cyclopropane-1,3'- pyrrolo[2,3-b]pyridin]-5'-yloxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[3-hydroxy-3-(2H3)methylcyclobutyl]-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[3-hydroxy-3-(2H3)methylcyclobutyl]-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)(1,1,2,2-2H4)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzodiazol-5- yl]oxy}(1,1,2,2-2H4)ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-indazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-indazol-5-yl]oxy}ethyl)-2- oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-3-(hydroxymethyl)-2-oxo-7- (trifluoromethyl)-2,3-dihydro-1H-1,3-benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H- 1,3-benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541157Docket No.: 79275-20025.40 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-3-(hydroxymethyl)-2-oxo-7-(trifluoromethyl)-2,3- dihydro-1H-1,3-benzodiazol-5-yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-7-(trifluoromethyl)-1H-imidazo[4,5- b]pyridin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; and 5-chloro-1'-(2-{3-[(3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-3H-1,3,5-triazainden-6- yloxy}ethyl)spiro[indoline-3,4'-piperidin]-2-one.

[0152] In some embodiments, a compound of formula (I) is selected from the group consisting of: 5-chloro-1'-(2-{[2-(1-methanesulfonylethyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(1S)-1-methanesulfonylethyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(1R)-1-methanesulfonylethyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethoxy)-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5,7-dichloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 7-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-7-carbonitrile; 5-chloro-1'-[(2S)-1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[(2S)-2-(4-methanesulfonylphenoxy)propyl]-1,2-dihydrospiro[indole-3,4'-piperidin]- 2-one;ny-2734541158Docket No.: 79275-20025.40 1'-[(2S)-1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 1'-[(2S)-2-(4-methanesulfonylphenoxy)propyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(3-methanesulfonylpropyl)-1H-indazol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(oxetan-3-yl)-1H-indazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{[1-(propan-2-yl)-1H-indazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-(4-{[(cis)-3-hydroxycyclobutyl]sulfonyl}phenoxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1-(2-hydroxyethyl)-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-[(cis)-3-hydroxycyclobutyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2-methoxyethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2-methoxyethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(oxetan-3-yl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[4-(3-methanesulfonylpropanesulfonyl)phenoxy]ethyl}-1-methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-bromo-1-(2-hydroxyethyl)-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(2-methoxyethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1-[2-(4-methanesulfonylphenoxy)ethyl]-1',2'-dihydrospiro[azepane-4,3'-indol]-2'-one; 5-chloro-1'-{2-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1-methyl-1'-{2-[(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541159Docket No.: 79275-20025.40 1-methyl-1'-{2-[(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1-methyl-1'-{2-[4-(1-methyl-1H-pyrazol-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-(2-{1-methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,3-dihydro-1λ⁶- benzothiophene-1,1-dione; 1-methyl-1'-{2-[(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1-methyl-1'-[2-(quinoxalin-6-yloxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1-methyl-1'-{2-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{2-[(1-acetyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1-methyl-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1-methyl-1'-{2-[4-(2-oxopyrrolidin-1-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]- 2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{4-[(1S)-1-methanesulfonylethyl]phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-(2-{4-[(1R)-1-methanesulfonylethyl]phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[4-(3-methanesulfonylpropanesulfonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-[2-(3,5-difluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 5-chloro-1'-{2-[4-(cyclopropanesulfonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-difluoromethanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)benzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzamide; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)pyridine-2- carboxamide;ny-2734541160Docket No.: 79275-20025.40 5-chloro-1'-[2-(2-fluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-methylbenzamide; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- methanesulfonylbenzonitrile; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N,N- dimethylpyridine-2-carboxamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methylbenzamide; 5-chloro-1'-{2-[(1-methanesulfonyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-methanesulfonyl-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(2-methanesulfonyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-1-methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(1-acetyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-5-chloro-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-{2-[(2-acetyl-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-5-chloro-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{2-[(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-1-methyl-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-{2-[(1-acetyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-1,2,3,4- tetrahydroquinoline-1-carboxamide; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-2,3- dihydro-1H-isoindole-2-carboxamide; 5-chloro-1'-[2-(quinoxalin-6-yloxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(3-fluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[(6-methanesulfonylpyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one;ny-2734541161Docket No.: 79275-20025.40 1'-[2-(4-methanesulfonylphenoxy)ethyl]-5-methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-1H-indazol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2- one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(1-methyl-1H-indazol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5- carbonitrile; 5-bromo-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-``one; 1'-[2-(4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(3-fluoro-4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; N-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N- methylmethanesulfonamide; N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N- methylmethanesulfonamide; 1'-[2-(4-{[dimethyl(oxo)-λ⁶-sulfanylidene]amino}phenoxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(8-methyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(8-methyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[(8-acetyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-5-chloro-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(8-acetyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 2-oxo-1'-{2-[(1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[3,5-difluoro-4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile;ny-2734541162Docket No.: 79275-20025.40 5-chloro-1'-[2-({1-[(cis)-3-hydroxycyclobutyl]-1H-indazol-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(trans)-3-hydroxycyclobutyl]-1H-indazol-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(1H-indazol-5-yloxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(1-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(3,5-difluoro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(3,5-difluoro-4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; methyl 1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)benzenesulfonyl]cyclopropane-1-carboxylate; 5-chloro-1'-(2-{4-[(3-methyloxetan-3-yl)sulfonyl]phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-(2-{4-[(3-methyloxetan-3-yl)sulfonyl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(2-methanesulfonyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 2-oxo-1'-(2-{[2-oxo-1-(propan-2-yl)-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-oxo-1-(propan-2-yl)-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N-(2- hydroxyethyl)methanesulfonamide; 5-chloro-1'-(2-{[1-(oxetan-3-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[4-(1-methanesulfonylcyclopropyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile;ny-2734541163Docket No.: 79275-20025.40 5-chloro-1'-{2-[4-(1-methanesulfonylcyclopropyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-1-methyl-3,4- dihydro-1H-2λ⁶,1-benzothiazine-2,2-dione; 1'-{2-[(1-methyl-2,2-dioxo-3,4-dihydro-1H-2λ⁶,1-benzothiazin-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[1-(2,2-difluoroethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(2,2-difluoroethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-methanesulfonyl-3-(trifluoromethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-methanesulfonyl-3-(trifluoromethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-[2-(4-methanesulfonyl-3-methylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-methanesulfonyl-3-methylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-[2-(4-difluoro-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-difluoromethanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]- 5-carbonitrile; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxycyclobutyl]-1,2,3,4-tetrahydroquinolin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; (S)-5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; (R)-5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541164Docket No.: 79275-20025.40 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (S)-2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (R)-2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-imidazo[4,3-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; (S)-5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; (R)-5-chloro-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({3-oxo-1H,2H,3H,5H,6H,10bH-pyrrolo[2,1-a]isoquinolin-8-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (S)-2-oxo-1'-(2-((3-oxo-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-8- yl)oxy)ethyl)spiro[indoline-3,4'-piperidine]-5-carbonitrile; (R)-2-oxo-1'-(2-((3-oxo-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-8- yl)oxy)ethyl)spiro[indoline-3,4'-piperidine]-5-carbonitrile; N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,6- difluorophenyl]-N-methylmethanesulfonamide; N-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,6- difluorophenyl]-N-methylmethanesulfonamide; 5-chloro-1'-[2-(4-methanesulfonyl-3,5-dimethylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(4-methanesulfonyl-3,5-dimethylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile;ny-2734541165Docket No.: 79275-20025.40 (S)-1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile ; (R)-1'-{2-[4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[3,5-difluoro-4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; (S)-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (R)-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[(6-methanesulfonyl-5-methylpyridin-3-yl)oxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; (S)-5-chloro-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; (R)-5-chloro-1'-{2-[3,5-difluoro-4-(1-methanesulfonylethyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-(2-{[2-oxo-1-(propan-2-yl)-2,3-dihydro-1H-indol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-oxo-1-(propan-2-yl)-2,3-dihydro-1H-indol-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; (S)-5-chloro-1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; (R)-5-chloro-1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541166Docket No.: 79275-20025.40 1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; (S)-1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (R)-1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-methyl-3,4- dihydro-2H-1λ⁶,2-benzothiazine-1,1-dione; 1'-{2-[(2-methyl-1,1-dioxo-3,4-dihydro-2H-1λ⁶,2-benzothiazin-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-(3-chloro-4-methanesulfonylphenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[2-(3-chloro-4-methanesulfonylphenoxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 1'-{2-[4-(1-cyano-1-methylethyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]- 5-carbonitrile; 5-chloro-1'-[2-({6-[(3-methyloxetan-3-yl)sulfonyl]pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1-(2-hydroxyethyl)-1'-{2-[4-methanesulfonyl-3-(trifluoromethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1-(2-hydroxyethyl)-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(6-methanesulfonyl-5-methylpyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[1-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-(difluoromethoxy)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-{2-[3-(difluoromethoxy)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)-3-(trifluoromethyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541167Docket No.: 79275-20025.40 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)-3-(trifluoromethyl)phenoxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-3,4-dihydro-2H- 1λ⁶,2-benzothiazine-1,1-dione; 1'-{2-[(1,1-dioxo-3,4-dihydro-2H-1λ⁶,2-benzothiazin-6-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[(7-fluoro-1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 2-oxo-1'-{2-[(1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[(1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-({2-[(3-methyloxetan-3-yl)oxy]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-({2-[(3-methyloxetan-3-yl)oxy]pyrimidin-5-yl}oxy)ethyl]-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-(2-{4-[3-(ethanesulfonyl)oxetan-3-yl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-1λ⁶- thiolane-1,1-dione; (S)-2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-1λ⁶- thiolane-1,1-dione; (R)-2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-1λ⁶- thiolane-1,1-dione; 1'-{2-[4-(1,1-dioxo-1λ⁶-thiolan-2-yl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-(2-{3-oxo-3H-spiro[2-benzofuran-1,3'-oxetan]-5-yloxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{2-[4-(1-methanesulfonylcyclobutyl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile;ny-2734541168Docket No.: 79275-20025.40 5-chloro-1'-[2-(4-{6-methanesulfonyl-2-oxaspiro[3.3]heptan-6-yl}phenoxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-(4-{6-methanesulfonyl-2-oxaspiro[3.3]heptan-6-yl}phenoxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-(2,2,2-trifluoroethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; N-(4-{2-[5-chloro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl]ethoxy}-2-(trifluoromethyl)phenyl)methanesulfonamide; 1'-{2-[4-(4-methanesulfonyloxan-4-yl)phenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole-3,4'- piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(4-methanesulfonyloxan-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-{2-[3,5-difluoro-4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-methyl-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[6-(2-methanesulfonylpropan-2-yl)pyridin-3-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[8-(2-hydroxyethyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; N-{2-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)benzenesulfonyl]ethyl}-N-methylacetamide; 1'-{2-[(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]ethyl}-5-chloro-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,3-dihydro-1λ⁶- benzothiophene-1,1-dione; 5-chloro-1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one;ny-2734541169Docket No.: 79275-20025.40 5-chloro-1'-{2-[4-(2-hydroxyethanesulfonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; chloro-1'-[(2S)-1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; chloro-1'-[(2R)-1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (S)-1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (R)-1'-{1-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[1-(4-methanesulfonylphenoxy)propan-2-yl]-1-[3-hydroxycyclobutyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[(2S)-1-(4-methanesulfonylphenoxy)propan-2-yl]-1-[(cis)-3-hydroxycyclobutyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[(2S)-1-(4-methanesulfonylphenoxy)propan-2-yl]-1-[(trans)-3-hydroxycyclobutyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[(2R)-1-(4-methanesulfonylphenoxy)propan-2-yl]-1-[(cis)-3-hydroxycyclobutyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[(2R)-1-(4-methanesulfonylphenoxy)propan-2-yl]-1-[(trans)-3-hydroxycyclobutyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[(2S)-1-[3-(difluoromethyl)-4-methanesulfonylphenoxy]propan-2-yl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[(2S)-1-[(1-methyl-1H-indazol-5-yl)oxy]propan-2-yl]-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 1'-[(2S)-1-[3-(difluoromethyl)-4-methanesulfonylphenoxy]propan-2-yl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-[(2S)-1-(3,5-difluoro-4-methanesulfonylphenoxy)propan-2-yl]-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile;ny-2734541170Docket No.: 79275-20025.40 N-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl}ethoxy)phenyl]methanesulfonamide; 5-chloro-1'-[2-(4-{[(trans)-3-hydroxycyclobutyl]sulfonyl}phenoxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-(1,2-dihydroxyethyl)-4-methanesulfonylphenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{3-[(1S)-1,2-difluoroethyl]-4-methanesulfonylphenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{3-[(1R)-1,2-difluoroethyl]-4-methanesulfonylphenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[3-(1,2-difluoroethyl)-4-methanesulfonylphenoxy]ethyl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 1'-(2-{3-[(1S)-1,2-difluoroethyl]-4-methanesulfonylphenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{3-[(1R)-1,2-difluoroethyl]-4-methanesulfonylphenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-methanesulfonyl-3-(oxetan-3-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(trans)-3-hydroxycyclobutyl]-1,2,3,4-tetrahydroquinolin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-{[1-(hydroxymethyl)cyclopropyl]sulfonyl}phenoxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)benzenesulfonyl]- N-methylcyclopropane-1-carboxamide; 1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)benzenesulfonyl]- N,N-dimethylcyclopropane-1-carboxamide; 1'-[2-(4-{[1-(azetidine-1-carbonyl)cyclopropyl]sulfonyl}phenoxy)ethyl]-5-chloro-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluoro-N- methylbenzamide;ny-2734541171Docket No.: 79275-20025.40 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluoro-N,N- dimethylbenzamide; 5-chloro-1'-{2-[3-fluoro-4-(morpholine-4-carbonyl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 4-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzoyl]- 1λ⁶-thiomorpholine-1,1-dione; 5-chloro-1'-{2-[3-fluoro-4-(3-methanesulfonylazetidine-1-carbonyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-(azetidine-1-carbonyl)-3-fluorophenoxy]ethyl}-5-chloro-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-{2-[3-fluoro-4-(3-hydroxyazetidine-1-carbonyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[4-(3-aminoazetidine-1-carbonyl)-3-fluorophenoxy]ethyl}-5-chloro-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; N-{1-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- fluorobenzoyl]azetidin-3-yl}methanesulfonamide; 4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzamide; 6-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2-fluorobenzoyl]- 2λ⁶-thia-6-azaspiro[3.3]heptane-2,2-dione; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-(1,1-dioxo-1λ⁶- thian-4-yl)-2-fluorobenzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-(1,1-dioxo-1λ⁶- thiolan-3-yl)-2-fluorobenzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-[(3S)-1,1-dioxo- 1λ⁶-thiolan-3-yl]-2-fluorobenzamide; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-[(3R)-1,1-dioxo- 1λ⁶-thiolan-3-yl]-2-fluorobenzamide; 5-chloro-1'-{2-[4-(3-methyl-1H-pyrazol-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 6-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-1,2,3,4- tetrahydroisoquinoline-2-carboxamide; 6-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-N-methyl-1,2,3,4- tetrahydroisoquinoline-2-carboxamide;ny-2734541172Docket No.: 79275-20025.40 5-chloro-1'-[2-({3-methyl-2-oxo-1H,2H,3H-imidazo[4,5-b]pyridin-6-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(6-{[1-(hydroxymethyl)cyclopropyl]sulfonyl}pyridin-3-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- (difluoromethyl)benzamide; 4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- (difluoromethyl)benzamide; 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-methyl-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{4-[3-(3-fluoroazetidine-1-carbonyl)oxetan-3-yl]phenoxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{4-[3-(azetidine-1-carbonyl)oxetan-3-yl]phenoxy}ethyl)-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile; 3-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N,N- dimethyloxetane-3-carboxamide; 3-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-N- methyloxetane-3-carboxamide; 5-chloro-1'-{2-[(7-fluoro-2-oxo-2,3-dihydro-1H-indol-5-yl)oxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 2-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)phenyl]-2- methylpropanamide; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)pyrimidine-2- carboxamide; 4-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2,6- difluorobenzoyl]-1λ⁶-thiomorpholine-1,1-dione; 1'-{2-[4-(1,1-dioxo-1λ⁶-thiomorpholine-4-carbonyl)-3,5-difluorophenoxy]ethyl}-1-methyl-2- oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{2-[4-(1,1-dioxo-1λ⁶-thiomorpholine-4-carbonyl)-3-(trifluoromethyl)phenoxy]ethyl}-1- methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2-dihydrospiro[indole- 3,4'-piperidine]-5-carbonitrile;ny-2734541173Docket No.: 79275-20025.40 (S)-1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; (R)-1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-1-(2-hydroxyethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-{2-[3-(difluoromethyl)-4-methanesulfonylphenoxy]ethyl}-1-(2-hydroxyethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(3-hydroxy-1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{4-[(cis)-3-hydroxy-1-methanesulfonylcyclobutyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{4-[(trans)-3-hydroxy-1-methanesulfonylcyclobutyl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 4-(4-{2-[5-chloro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'- yl]ethoxy}-2-(trifluoromethyl)benzoyl)-1λ⁶-thiomorpholine-1,1-dione; 4-[4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-2- (trifluoromethyl)benzoyl]-1λ⁶-thiomorpholine-1,1-dione; 5-chloro-1'-[2-(3-fluoro-4-{6-methanesulfonyl-2,6-diazaspiro[3.3]heptane-2- carbonyl}phenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,4H-pyrido[2,3- d][1,3]oxazin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-ethyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541174Docket No.: 79275-20025.40 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-cyclopropyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-cyclopropyl-3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylazetidin-1-yl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[(cis)-3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[(trans)-3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro- 1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-{2-[(7-oxo-8-{[(cis)-3-hydroxy-3-methylcyclobutyl]methyl}-5,6,7,8- tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-{2-[(7-oxo-8-{[(trans)-3-hydroxy-3-methylcyclobutyl]methyl}-5,6,7,8- tetrahydro-1,8-naphthyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(7-oxo-8-{[(cis)-3-hydroxy-3-methylcyclobutyl]methyl}-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxyazetidin-1-yl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({8-[3-(hydroxymethyl)cyclobutyl]-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-(propan-2-yl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-ethyl-3-hydroxycyclobutyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-(difluoromethyl)-1'-[2-({8-[(3-hydroxy-3-methylcyclobutyl)methyl]-7-oxo-5,6,7,8-tetrahydro- 1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541175Docket No.: 79275-20025.40 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-ethyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(7-oxo-8-{[(trans)-3-hydroxy-3-methylcyclobutyl]methyl}-5,6,7,8-tetrahydro- 1,8-naphthyridin-3-yl)oxy]ethyl}-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethoxy)-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro- 1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[3-(hydroxymethyl)cyclobutyl]-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[(3-hydroxy-3-methylcyclobutyl)methyl]-7-oxo-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethoxy)-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-7-iodo-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-hydroxy-3-(propan-2-yl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-(hydroxymethyl)cyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[6-(1-hydroxyethyl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one ; 1'-(2-{[6-(1-hydroxyethyl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[5-(difluoromethyl)-7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro- 1,8-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[5-(difluoromethyl)-7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]- 7,8-dihydro-1,8-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5-(trifluoromethyl)-7,8-dihydro- 1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541176Docket No.: 79275-20025.40 5-(difluoromethyl)-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5-(trifluoromethyl)- 7,8-dihydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3- b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H- pyrrolo[2,3-b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(trans)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3- b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({2-oxo-1-[(trans)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H- pyrrolo[2,3-b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H-pyrido[2,3-d]pyrimidin- 6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H,4H-pyrido[2,3- d]pyrimidin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrazolo[3,4-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-oxo-4-[(cis)-3-hydroxy-3-methylcyclobutyl]-3H,4H-pyrido[2,3-b]pyrazin-7- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[4-(3-hydroxy-3-methylcyclobutyl)pyrido[3,2-d]pyrimidin-7-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylcyclobutyl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxy-3-methylazetidin-1-yl)pyrido[2,3-d]pyridazin-3-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[4-(3-hydroxy-3-methylazetidin-1-yl)pyrido[3,2-d]pyrimidin-7-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(3-hydroxyazetidin-1-yl)pyrido[2,3-d]pyridazin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541177Docket No.: 79275-20025.40 5-chloro-1'-(2-{[4-(3-hydroxyazetidin-1-yl)pyrido[3,2-d]pyrimidin-7-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-[(cis)-3-hydroxy-3-methylcyclobutyl]-3H-imidazo[4,5-b]pyridin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({2-oxo-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-imidazo[4,5- b]pyridin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[3-(hydroxymethyl)azetidin-1-yl]-1,7-naphthyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-({6-[(1S)-1-hydroxyethyl]-5-(trifluoromethyl)pyridin-3-yl}oxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3 ,4'-piperidine]-5-carbonitrile ; 1'-[2-({6-[(1R)-1-hydroxyethyl]-5-(trifluoromethyl)pyridin-3-yl}oxy)ethyl]-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({2-[(1S)-1,2-dihydroxyethyl]pyrimidin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(1R)-1,2-dihydroxyethyl]pyrimidin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(2S)-1,2-dihydroxypropan-2-yl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(2R)-1,2-dihydroxypropan-2-yl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(1S)-1,2-dihydroxyethyl]-5-(trifluoromethyl)pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(1R)-1,2-dihydroxyethyl]-5-(trifluoromethyl)pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(2S)-1,2-dihydroxypropan-2-yl]-5-(trifluoromethyl)pyridin-3-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(2R)-1,2-dihydroxypropan-2-yl]-5-(trifluoromethyl)pyridin-3-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[(cis)-3-hydroxy-3-methylcyclobutyl]-1,7-naphthyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[(trans)-3-hydroxy-3-methylcyclobutyl]-1,7-naphthyridin-3-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541178Docket No.: 79275-20025.40 5-chloro-1'-[2-({4-[(cis)-3-hydroxy-3-methylcyclobutyl]pyrido[3,2-d]pyrimidin-7-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({4-[(trans)-3-hydroxy-3-methylcyclobutyl]pyrido[3,2-d]pyrimidin-7- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[(cis)-3-hydroxy-3-methylcyclobutyl]pyrido[2,3-d]pyridazin-3-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({8-[(trans)-3-hydroxy-3-methylcyclobutyl]pyrido[2,3-d]pyridazin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(cis)-3-hydroxy-3-methylcyclobutyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(trans)-3-hydroxy-3-methylcyclobutyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-2H,3H-[1,3]oxazolo[4,5- b]pyridin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-{6-hydroxy-2-azaspiro[3.3]heptan-2-yl}pyrimidin-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(3-ethyl-3-hydroxyazetidin-1-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-cyclopropyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[6-(1-hydroxyethyl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5,7-dichloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1,2-dihydroxyethyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-({2-[1-(hydroxymethyl)cyclopropyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-hydroxy-2-methylpropan-2-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541179Docket No.: 79275-20025.40 5-chloro-1'-(2-{[5-(difluoromethyl)-7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro- 1,8-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-(2-{[5-(difluoromethyl)-7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]- 7,8-dihydro-1,8-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5-(trifluoromethyl)-7,8-dihydro- 1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5-(trifluoromethyl)- 7,8-dihydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{4-[1-(dimethylphosphoryl)cyclopropyl]phenoxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[1-(dimethylphosphoryl)cyclopropyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(1r,3s)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-pyrrolo[2,3- b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H- pyrrolo[2,3-b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzodiazol-5-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,2,3,4- tetrahydroquinolin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,2,3,4- tetrahydroquinolin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({2-oxo-1-[(1r,3s)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H,4H-pyrido[2,3- d]pyrimidin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrazolo[3,4-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-oxo-4-[(cis)-3-hydroxy-3-methylcyclobutyl]-3H,4H-pyrido[2,3-b]pyrazin-7- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({3-[(cis)-3-hydroxy-3-methylcyclobutyl]-3H-imidazo[4,5-b]pyridin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541180Docket No.: 79275-20025.40 5-chloro-1'-(2-{[6-(2-hydroxypropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(3-hydroxy-3-methylcyclobutyl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H,2H,3H-imidazo[4,5- b]pyridin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(1R or 1S)-1,2-dihydroxyethyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one ; 5-chloro-1'-[2-({2-[(1S or 1R)-1,2-dihydroxyethyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(cis)-3-hydroxy-3-methylcyclobutyl]pyrimidin-5-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(cis) or (trans)-3-hydroxy-3-methylcyclobutyl]pyrimidin-5-yl}oxy)ethyl]- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[6-(1-hydroxy-2-methanesulfonylpropan-2-yl)-5-(trifluoromethyl)pyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(2S or 2R)-1-hydroxy-2-methanesulfonylpropan-2-yl]-5- (trifluoromethyl)pyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({6-[(2R or 2S)-1-hydroxy-2-methanesulfonylpropan-2-yl]-5- (trifluoromethyl)pyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[6-(3-hydroxy-3-methylazetidin-1-yl)-5-(trifluoromethyl)pyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({7-oxo-8-[( cis)-3-hydroxy-3-methylcyclobutyl]-7,8-dihydro-1,8-naphthyridin-3- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(trans)-3-hydroxy-3-methylcyclobutyl]-1H-pyrazolo[3,4-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5,7-dichloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541181Docket No.: 79275-20025.40 2-oxo-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrrolo[2,3-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[6-(2-hydroxypropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(1-methanesulfonylpiperidin-4-yl)phenoxy]ethyl}-1-(²H₃)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(²H₃)methyl-1'-(2-{4-[methyl(methylimino)oxo-λ⁶-sulfanyl]-3- (trifluoromethyl)phenoxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(²H₃)methyl-1'-(2-{4-[3-(propane-2-sulfonyl)oxetan-3-yl]phenoxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[4-(1-methanesulfonylcyclobutyl)phenoxy]ethyl}-1-(²H₃)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(²H₃)methyl-1'-{2-[(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)oxy]ethyl}-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(2-hydroxy-2-methylpropyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1-(²H₃)methyl-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-(4-methanesulfonylphenoxy)ethyl]-1-(²H₃)methyl-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1-(²H₃)methyl-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8- tetrahydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[1-(hydroxymethyl)cyclopropyl]pyrimidin-5-yl}oxy)ethyl]-1-(²H₃)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 6-{2-[5-chloro-1-(²H₃)methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl]ethoxy}-8- fluoro-3,4-dihydro-2H-1λ⁶,2-benzothiazine-1,1-dione; 5-chloro-1'-(2-{[2-(3-methanesulfonyloxetan-3-yl)pyrimidin-5-yl]oxy}ethyl)-1-(²H₃)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1-(²H₃)methyl-1'-[2-({7-oxo-8-[(cis)-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1-(²H₃)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-methanesulfonylethyl)pyrimidin-5-yl]oxy}ethyl)-1-(²H₃)methyl-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541182Docket No.: 79275-20025.40 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)(1,1,2,2-²H₄)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-2H-indazol-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-2H-indazol-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-(3-hydroxyoxetan-3-yl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(1-hydroxycyclobutyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 1'-(2-{[6-(3-hydroxy-3-methylazetidin-1-yl)-5-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[2-(1-hydroxy-2-methylpropan-2-yl)pyrimidin-5-yl]oxy}ethyl)-2-oxo-1,2- dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 2-oxo-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzodiazol- 5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,2,3- benzotriazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,2,3- benzotriazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 2-oxo-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-pyrazolo[3,4-b]pyridin-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 1'-(2-{[1-(3-hydroxy-3-methylcyclobutyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]oxy}ethyl)-2-oxo- 1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidin]-1'-yl}ethoxy)-1-[(cis)-3-hydroxy- 3-methylcyclobutyl]-1H-1,3-benzodiazole-7-carbonitrile; 5-chloro-1'-[2-({3-[(cis)-3-hydroxy-3-methylcyclobutyl]-3H-[1,2,3]triazolo[4,5-b]pyridin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[2-(2,2-dimethyl-1,3-dioxolan-4-yl)pyrimidin-5-yl]oxy}ethyl)-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one;ny-2734541183Docket No.: 79275-20025.40 5-chloro-1'-[2-({2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-({2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl}oxy)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-{2-[4-(1-methanesulfonylpiperidin-4-yl)phenoxy]ethyl}-1,2-dihydrospiro[indole- 3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[7-(difluoromethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[7-(difluoromethyl)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[7-(difluoromethoxy)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3- benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[7-(difluoromethoxy)-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzodiazol-5- yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-(2-{[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]oxy}ethyl)-7-iodo-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-(difluoromethyl)-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({2-methyl-3-[(cis)-3-hydroxy-3-methylcyclobutyl]-3H-imidazo[4,5-b]pyridin-6- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[8-(2-hydroxy-2-methylpropyl)-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3- yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-7-iodo-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzodiazol-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-[2-({7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzodiazol-5-yl}oxy)ethyl]-2- oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,2,3,4- tetrahydroquinazolin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-8-(trifluoromethyl)-1,2,3,4- tetrahydroquinazolin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile;ny-2734541184Docket No.: 79275-20025.40 5-chloro-1'-[2-({7,7-dimethyl-5-oxo-5H,7H-furo[3,4-b]pyridin-3-yl}oxy)ethyl]-1,2- dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-{2-[(2-{6-hydroxy-6-methyl-2-azaspiro[3.3]heptan-2-yl}pyrimidin-5-yl)oxy]ethyl}- 1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{2'-oxo-1'-[(cis)-3-hydroxy-3-methylcyclobutyl]-1',2'-dihydrospiro[cyclopropane- 1,3'-pyrrolo[2,3-b]pyridin]-5'-yloxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-(²H₃)methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-(²H₃)methylcyclobutyl]-5,6,7,8-tetrahydro-1,8- naphthyridin-3-yl}oxy)(1,1,2,2-²H₄)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl}oxy)(1,1,2,2-²H₄)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 2-oxo-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5- yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({2-[(1r,3s)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3- benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{[3-(hydroxymethyl)-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7- (trifluoromethyl)-2,3-dihydro-1H-1,3-benzodiazol-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'- piperidin]-2-one; 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-2,3-dihydro- 1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 1'-(2-{[3-(hydroxymethyl)-2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)- 2,3-dihydro-1H-1,3-benzodiazol-5-yl]oxy}ethyl)-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]- 5-carbonitrile; 2-oxo-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-2,3-dihydro- 1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4’-piperidine]-5-carbonitrile; 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-imidazo[4,5- b]pyridin-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one; 5-chloro-1'-(2-{3-[(cis)-3-hydroxy-3-methylcyclobutyl]-4-(trifluoromethyl)-3H-1,3,5- triazainden-6-yloxy}ethyl)spiro[indoline-3,4'-piperidin]-2-one,ny-2734541185Docket No.: 79275-20025.40 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0153] Compound Names disclosed herein, e.g. as included in the list in the paragraphs above, were generated ChemDraw®software version 18.1.0.458, ChemDraw®software version 18.0.0.231, or Collaborative Drug Discovery Inc. (CDD) CDD Vault update #3.

[0154] In some embodiments, a compound of formula (I) is selected from a compound of Table 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

[0155] Isotopically labeled forms of any of the foregoing are also embraced, such as deuterated or tritiated forms (wherein at least one hydrogen is replaced by at least one deuterium or tritium) of any of the specific compounds detailed herein. Mixtures of any of the foregoing are also embraced and described. Prodrugs of any of the foregoing are also embraced herein.

[0156] As a non-limiting example, compounds of formula (I), or any embodiment or variation thereof, are provided, wherein any one or more H atoms are replaced with deuterium. For example, compounds of formula (I), or any embodiment or variation thereof, are provided wherein L1is C1-6alkylene, wherein one or more H atoms of the C1-6alkylene are replaced with deuterium. For example, compounds of formula (I), or any embodiment or variation thereof, are provided wherein L1is -(CD2)1-6-. In some embodiments of the compound of formula (I), or any embodiment or variation thereof, L1is -(CD2)-(CD2)-.

[0157] In some embodiments, of the compounds of formula (I), the compounds of formula (I) contain one or more hydrogen atoms that are replaced with deuterium, wherein deuterium is present in an amount that is greater than its natural abundance. Thus, as used herein, designation of an atom as deuterium at a position indicates that the abundance of deuterium is significantly greater than the natural abundance of deuterium. Unless otherwise stated, when a position is designated specifically as “H” or “hydrogen,” the position is understood to have hydrogen at its naturally abundant isotopic composition. Also, unless otherwise stated, when a position is designated specifically as “D” or “deuterium,” the position is understood to have deuterium at an abundance that is significantly greater than the natural abundance of deuterium, e.g., at least 3000 times greater than the natural abundance of deuterium, which is about 0.015% (i.e., the term “D” or “deuterium” indicates at least about 45% incorporation of deuterium).

[0158] In some embodiments, the compounds provided herein inhibit APOL1 at a concentration of less than 10 μM, less than 1 μM, less than 0.5 μM, or less than 0.1 μM. In someny-2734541186Docket No.: 79275-20025.40 embodiments, the compounds provided herein inhibit APOL1 at a concentration of 1 to 10 μM, 0.01 to 1 μM, or 0.01 to 10 μM.

[0159] In some embodiments, the compounds provided herein reduce cell death caused by overexpression of APOL1. In some embodiments, the compounds provided herein reduce cell death caused by overexpression APOL1 at a concentration of less than 10 μM, less than 1 μM, less than 0.5 μM, or less than 0.1 μM. In some embodiments, the compounds provided herein reduce cell death caused by APOL1 overexpression at a concentration of 1 to 10 μM, 0.01 to 1 μM, or 0.01 to 10 μM.

[0160] In some embodiments, compounds provided herein have an EC50of less than 1 μM, less than 0.5 μM, or less than 0.1 μM. In some embodiments, the compounds provided herein have an EC50of 1 to 10 μM, 0.01 to 1 μM, or 0.01 to 10 μM.

[0161] In some embodiments, compounds provided herein have an AC50of less than 1 μM, less than 0.5 μM, or less than 0.1 μM. In some embodiments, the compounds provided herein have an AC50of 1 to 10 μM, 0.01 to 1 μM, or 0.01 to 10 μM. In some embodiments, the AC50value reflects the compound’s ability to prevent calcium influx by inhibiting APOL1.

[0162] In some embodiments, the compounds provided herein inhibit a cation channel. In some embodiments, the compounds of the present disclosure inhibit a calcium channel. In some embodiments, the compounds of the present disclosure reduce calcium transport.

[0163] In some embodiments, the APOL1 risk allele is a G0 variant. In some embodiments, the G0 variant is G0 E150 (p.K150E). KITS

[0164] The present disclosure further provides kits for carrying out the methods of the invention. The kits may comprise a compound or pharmaceutically acceptable salt thereof as described herein and suitable packaging. The kits may comprise one or more containers comprising any compound described herein. In one aspect, a kit includes a compound of the disclosure or a pharmaceutically acceptable salt thereof, and a label and / or instructions for use of the compound in the treatment of a disease or disorder described herein. The kits may comprise a unit dosage form of the compound.

[0165] Provided herein are kits, comprising (i) a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) instructions for use in treating diabetic retinopathy in an individual in need thereof. Also provided herein are kits, comprisingny-2734541187Docket No.: 79275-20025.40 (i) a pharmaceutical composition comprising a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, 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 diabetic retinopathy in an individual in need thereof. In some embodiments, 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. In some embodiments, the administration comprises oral administration or intravitreal injection. In some embodiments, the administration comprises oral administration. In some embodiments, the administration comprises intravitreal injection. In some embodiments, the method further comprises 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 subject.

[0166] Provided herein are kits, comprising (i) a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) instructions for use in preventing and / or delaying the development of diabetic retinopathy in an individual in need thereof. Also provided herein are kits, comprising (i) a pharmaceutical composition comprising a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, 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 preventing and / or delaying the development of diabetic retinopathy in an individual in need thereof. Provided herein are kits, comprising (i) a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) instructions for use in delaying the development of diabetic retinopathy in an individual in need thereof. Also provided herein are kits, comprising (i) a pharmaceutical composition comprising a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, 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 delaying the development of diabetic retinopathy in an individual in need thereof. In some embodiments, 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. In some embodiments, the administration comprises oral administration or intravitrealny-2734541188Docket No.: 79275-20025.40 injection. In some embodiments, the administration comprises oral administration. In some embodiments, the administration comprises intravitreal injection. In some embodiments, the method further comprises 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 subject.

[0167] Articles of manufacture are also provided, wherein the article of manufacture comprises a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in a suitable container. Also provided herein are articles of manufacture, comprising a pharmaceutical composition comprising a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in a suitable container. The container may be a vial, jar, ampoule, preloaded syringe, or intravenous bag. COMPOSITIONS

[0168] Provided herein are pharmaceutical compositions comprising one or more compounds of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, provided herein is a pharmaceutical composition comprising (i) a compound of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.

[0169] Suitable pharmaceutically acceptable excipients may include, for example, fillers, diluents, sterile aqueous solutions and various organic solvents, permeation enhancers, solubilizers, and adjuvants. Various substances may be embraced by the term excipient, including without limitation any substance used as a binder, disintegrant, coating, compression / encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspending / gelling agent, or wet granulation agent. Examples of suitable excipients are well-known to those skilled in the art. Such compositions are prepared in a manner well known in the pharmaceutical art. See, e.g., Handbook of Pharmaceutical Excipients, Pharmaceutical Press, 9thed. (2020), and Remington’s Pharmaceutical Sciences, Academic Press, 23rded. (2020), each of which is incorporated herein by reference in its entirety.ny-2734541189Docket No.: 79275-20025.40

[0170] The pharmaceutical compositions may be administered in either single or multiple doses. The pharmaceutical composition may be administered by various methods including, for example, oral, rectal, buccal, intranasal, and transdermal routes. In certain embodiments, the pharmaceutical composition may be administered by intra-arterial injection, intravenously, intraperitoneally, parenterally, intramuscularly, subcutaneously, orally, topically, or as an inhalant. In some embodiments, the administration is oral administration.

[0171] Compounds as described herein may be administered to individuals in a form of generally accepted oral compositions, such as tablets, coated tablets, gel capsules in a hard or in soft shell, emulsions or suspensions. Examples of carriers, which may be used for the preparation of such compositions, are lactose, corn starch or its derivatives, talc, stearate or its salts, etc. Acceptable carriers for gel capsules with soft shell are, for instance, plant oils, wax, fats, semisolid and liquid poly-ols, and so on. In addition, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, re-wetting agents, emulgators, sweeteners, dyes, adjusters, salts for the adjustment of osmotic pressure, buffers, coating agents or antioxidants.

[0172] The specific dose level of a compound as described herein will depend upon a variety of factors such as the age, body weight and sex of the individual as well as the route of administration and other factors. In some embodiments, a dosage is expressed as a number of milligrams of a compound described herein per kilogram of the individual’s body weight (mg / kg). Dosages of between about 0.1 mg / kg and 100-150 mg / kg may be appropriate.

[0173] The compound may be administered to an individual in accordance with an effective dosing regimen for a desired period of time or duration, such as at least about one month, at least about 2 months, at least about 3 months, at least about 6 months, or at least about 12 months or longer, which in some variations may be for the duration of the individual’s life. EXAMPLES

[0174] The following synthetic reaction schemes, which are detailed in the Schemes, General Procedures, and Examples, are merely illustrative of some of the methods by which the compounds of the present disclosure, or an embodiment or aspect thereof, can be synthesized. Various modifications to these synthetic reaction schemes can be made, as will be apparent to those of ordinary skill in the art.

[0175] The starting materials and the intermediates of the synthetic reaction schemes can be isolated and purified if desired using conventional techniques, including but not limited to,ny-2734541190Docket No.: 79275-20025.40 filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectral data.

[0176] Although certain exemplary embodiments are depicted and described herein, the compounds of the present disclosure, or any variation or embodiment thereof, may be prepared using appropriate starting materials according to the methods described generally herein and / or by methods available to one of ordinary skill in the art. Synthetic Examples

[0177] As depicted in the Schemes, General Procedures, and Examples below, in certain exemplary embodiments, compounds of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, are prepared according to the general procedures. The general methods below, and other methods known to synthetic chemists of ordinary skill in the art, can be applied to all formulae, variations, embodiments, and species described herein. Scheme 1

[0178] Compounds of formula S1-3 may be prepared according to Scheme 1. Alkylation of amine S1-2 with an alkyl halide such as S1-1 in the presence of an inorganic base such as potassium carbonate and a polar aprotic solvent such as DMF provides compound S1-3. In cases where L3 represents a chiral atom, compound S1-3 may be further purified by chiral SFC to deliver single stereoisomers. Scheme 2ny-2734541191Docket No.: 79275-20025.40

[0179] Compounds of formula S2-3 may be prepared may also be prepared by coupling a phenol or heterocyclic variant such as S2-1 with an alcohol such as S2-2 in the presence of triphenylphosphine and DIAD in an aprotic solvent such as THF, as depicted in Scheme 2. Alternative Mitsunobu-type reaction conditions with polymer-bound triphenylphosphine and DIAD in toluene may also be used to generate compounds of formula S2-3. Scheme 3

[0180] As outlined in Scheme 3, compounds of formula S3-3 may be prepared from alkyl chlorides such as S3-1 and amine S3-2 by heating in an aprotic solvent such as DMF in the presence of sodium iodide and an inorganic base such as potassium carbonate. Scheme 4

[0181] Compounds of formula S4-3 may also be prepared from phenol S4-1 and alkyl halide S4- 2 by heating in an aprotic solvent such as DMF in the presence of silver oxide, as shown in Scheme 4. Alternative reaction conditions involving potassium carbonate in DMF may also be used to generate compounds of formula S4-3. Scheme 5ny-2734541192Docket No.: 79275-20025.40

[0182] Oxindoles such as S5-1 may be elaborated by reaction with an alkyl halide in the presence of an inorganic base such as potassium carbonate in DMF, at elevated temperature. This provides compounds such as S5-2, as depicted in Scheme 5. Scheme 6

[0183] Scheme 6 depicts an approach to compounds of formula S6-5. Alkylation of oxindole S6-1 with an alkyl halide in the presence of a base such as potassium carbonate generates S6-2. Removal of the Boc group by treatment with a protic acid such as TFA in an aprotic solvent such as DCM generates amine S6-3, which can be further elaborated by coupling with an alkyl halide such as S6-4, according to procedures shown in Scheme 1. Scheme 7ny-2734541193Docket No.: 79275-20025.40

[0184] An alternative approach to compounds of formula S7-3 involving reductive amination of ketone S7-2 with amine S7-2 under the action of sodium triacetoxyborohydride, titanium tetraisopropoxide and acetic acid, is depicted in Scheme 7. Scheme 8

[0185] Scheme 8 depicts an alternative approach to compounds of formula S8-6. Generation of benzylic chloride S8-2 from benzylic alcohol S8-1, followed by introduction of a sulfonyl group, gives rise to compound S8-3. Deprotection of S8-3 with in situ-formed TMSI gives phenol S8-4, which can be coupled with alkyl chloride S8-5 in the presence of potassium carbonate and sodium iodide in acetone at elevated temperature. Single stereoisomers may be obtained by chiral SFC purification of S8-6. Scheme 9

[0186] Scheme 9 shows an approach to compounds of formula S9-7. Alkylation of phenol S9-1 with ethylene oxide, followed by SNAr reaction with sodium methanethiolate gives thioether S9-ny-2734541194Docket No.: 79275-20025.40 3. Oxidation with mCPBA gives sulfone S9-4. Treatment of S9-4 with methanesulfonyl chloride and a tertiary amine base such as DIPEA gives S9-5, which can be converted to S9-7 under conditions similar to Scheme 1. Scheme 10

[0187] As shown in Scheme 10, compounds of formula S10-1 may be further elaborated via coupling with a sulfonyl chloride such as methanesulfonyl chloride in the presence of triethylamine in DCM to provide S10-2. Compound S10-1 may also be acylated with an anhydride such as acetic anhydride and triethylamine to generate S10-3. Scheme 11

[0188] As shown in Scheme 11, compounds of formula S11-1 may be elaborated via coupling with a carbamoyl chloride such as N-methylcarbamoyl chloride in the presence of triethylamine to give a urea of the formula S11-2. Scheme 12ny-2734541195Docket No.: 79275-20025.40

[0189] An alternative approach to compounds of formula S12-3 is depicted in Scheme 12, via coupling of a mesylate such as S12-1 and amine such as S12-2 in acetonitrile using sodium bicarbonate as base. Scheme 13

[0190] Scheme 13 depicts the conversion of cis isomer S13-1 to trans isomer S13-3. Mitsunobu coupling with p-nitrobenzoic acid generates ester S13-2, which can undergo hydrolysis with lithium hydroxide to generate the trans isomer S13-3. Scheme 14ny-2734541196Docket No.: 79275-20025.40

[0191] Elaboration of compounds of formula S14-1 (generated using methods described in Scheme 1) is depicted in Scheme 14. Cross coupling of S14-1 with potassium vinyltrifluoroborate using a palladium catalyst and an inorganic base provides olefin S14-2. Dihydroxylation with an osmium catalyst and NMO gives S14-3. Diol S14-3 may be further modified by treatment with DAST, giving rise to difluoride S14-4 as an isomeric mixture. Single isomer analogs such as S14-5 may be obtained by chiral SFC purification. Scheme 15

[0192] Iodide S15-1 may be elaborated using photoredox methods outlined in Scheme 15. Coupling of S15-1 and 3-iodooxetane can be achieved with nickel(I) chloride ethylene glycol dimethyl ether complex, ligand S15-2, (Ir[dF(CF3)ppy]2(dtbpy))PF6, bis(trimethylsilyl)silyl- trimethylsilane, Na2CO3and blue LED to generate S15-3. Scheme 16ny-2734541197Docket No.: 79275-20025.40

[0193] Conversion of cis-disubstituted cyclobutanol S16-1 to the trans isomer S16-4 is depicted in Scheme 16. Treatment with methanesulfonic anhydride and TEA generates mesylate S16-2. Heating with potassium acetate generates ester S16-3, which can be converted to the alcohol under the action of potassium carbonate in MeOH to give S16-4. Scheme 17

[0194] Compounds of the formula S17-1 can be converted to the corresponding alcohol by treatment with a reducing agent such as LiBH4, as depicted in Scheme 17. Alternatively, S17-1 can underdo hydrolysis with lithium hydroxide to give acid S17-3. Amide bond formation with an amine such as methylamine under the action of T3P and TEA generates amide S17-4. Scheme 18ny-2734541198Docket No.: 79275-20025.40

[0195] Compounds of formula S18-1 can be elaborated by Suzuki couplings of boronate esters such as S18-2, a catalyst such as bis(4-(di-tert-butylphosphanyl)-N,N-dimethylaniline) dichloropalladium, and a base such as KOAc, as depicted in Scheme 18. Scheme 19

[0196] Scheme 19 begins with protection of an oxindole nitrogen using sodium hydride and SEMCl to give S19-2. Coupling with a phenol such as S19-3 gives S19-4. Removal of the SEM group is achieved by heating a mixture of S19-4, potassium carbonate, and NaI in acetone to give compound of formula S19-5. Scheme 20ny-2734541199Docket No.: 79275-20025.40

[0197] Heterocyclic electrophiles bearing protecting groups such as compound S20-1 may be coupled with amine nucleophiles such as S20-2 under the conditions shown in Scheme 20. Deprotection of a protecting group such as a SEM N-O acetal may be achieved by treatment of S20-3 with a protic acid such as TFA to deliver S20-4. Scheme 21

[0198] An approach to compounds of formula S21-9 is shown in Scheme 21. Alkylation of thiol S21-1 followed by oxidation to the sulfone generates compound S21-3. Cyclopropane formation via double alkylation in the presence of potassium carbonate gives S21-4. SNAr reaction with ethylene glycol and mesylation of S21-5 provides compound S21-6, which can be coupled with amine S21-7 under standard conditions (Scheme 12). Treatment of compound S21-8 with a reducing agent such as LiAlH4gives compound S21-9. Scheme 22ny-2734541200Docket No.: 79275-20025.40

[0199] Compounds of formula S22-2 may be obtained by treatment of compound S22-1 with a base such as sodium hydride and an alkylating agent such as iodomethane, as depicted in Scheme 22. Scheme 23.

[0200] Primary amides of formula S23-7 can be generated according to Scheme 23. Palladium- catalyzed borylation of pyrimidine S23-1 followed by oxidation gives compound S23-3. Alkylation with 1,2-dibromoethane to provide S23-4 and coupling with amine S23-5 under conditions outlined above (Scheme 12) generates compound S23-6. Conversion of the nitrile to the primary amide S23-7 occurs upon treatment with potassium carbonate and aqueous H2O2. Scheme 24ny-2734541201Docket No.: 79275-20025.40

[0201] Compounds of formula S24-8 can be synthesized according to Scheme 24. Esterification and alkylation of carboxylic acid S24-1 provides alkyl bromide S24-3. Coupling with amine S24-4 under standard conditions (Scheme 12) gives S24-5. Hydrolysis followed by amide bond formation with amine S24-7, using N-methyl imidazole and TCFH, gives S24-8. Scheme 25

[0202] Compounds of formula S25-3 may also be prepared by reaction of an amine such as S25- 1 with a secondary mesylate such as S25-2 in the presence of NaHCO3and potassium iodide in DMF at elevated temperature, as depicted in Scheme 25. Compounds of formula S25-3 may be further purified by chiral SFC to generate isomerically pure analogs. Scheme 26ny-2734541202Docket No.: 79275-20025.40

[0203] Compounds of formula S26-10 may be prepared according to Scheme 26. Lithium- halogen exchange with aryl bromide S26-1, followed by addition to a ketone such as S26-2, gives alcohol S26-3 as a mixture of cis and trans isomers. Reaction with sodium methanesulfinate and TFA gives sulfone S26-4. Removal of benzyl ethers by hydrogenation gives diol S26-5. Selective alkylation of the phenol moiety with bromoethyl acetate gives ester S26-6. Reduction with LiAlH4gives alcohol S26-7, which can be converted to S26-8 and coupled with amine S26-9 using procedures described above (Scheme 12). Further purification of S26-10 to obtain single stereoiosmers may be achieved by methods such as reverse phase HPLC or chiral SFC. Scheme 27ny-2734541203Docket No.: 79275-20025.40

[0204] Compounds of formula S27-5 can be prepared according to Scheme 27. Coupling of acid S27-1 with an amine such as S27-2 under the action of EDCI and HOBt gives amide S27-3. Treatment with a protic acid such as TFA gives amine S27-4. Amine S27-4 may be further elaborated, such as by reaction with methanesulfonic anhydride and TEA, to give compounds such as S27-5. Scheme 28

[0205] Compounds of formula S28-3 can be prepared according to Scheme 28, using reaction conditions similar to those described above. Coupling of amine S28-1 with azatetrahydronaphthyridinones bearing tertiary alcohol moieties such S28-2 occurs upon heating in an aprotic solvent such as acetonitrile in the presence of an inorganic base such as sodium bicarbonate to give compounds of formula S28-3. Scheme 29ny-2734541204Docket No.: 79275-20025.40

[0206] Compounds of formula S29-4 may can be prepared according to Scheme 29. Reaction of amine S29-1 with an alkyl bromide bearing a secondary alcohol such as S29-2 occurs upon heating in an aprotic solvent such as acetonitrile in the presence of an inorganic base such as sodium bicarbonate to give compounds of formula S29-3. Further purification using methods such as chiral SFC may be used to generate single isomer analogs such as S29-4. Scheme 30

[0207] Compounds of formula S30-3 and S30-5, which bear multiple substituents on the pyrimidine moiety, are depicted in Scheme 30. Thus, coupling of the amine HCl salt S30-1 with alkyl halide S30-2 may be achieved upon heating in an aprotic solvent such as DMF, in the presence of potassium carbonate and potassium iodide, to deliver compounds of formula 30-3.ny-2734541205Docket No.: 79275-20025.40 Alternatively, coupling under identical reaction conditions as those described above with amine S30-1 and a chiral center bearing intermediate such as S30-4, may give rise to compounds of the formula S30-5. If desired, further purification of S30-5 may be achieved using methods such as chiral SFC. Scheme 31ny-2734541206Docket No.: 79275-20025.40

[0208] Compounds of formula S31-12 may be prepared according to Scheme 31. Treatment of indazole S31-1 with iodine and potassium hydroxide in a solvent such as DMF provides S31-2. Alkylation of S31-2 with an electrophile such as S31-3 occurs in the presence of an inorganic base such as potassium carbonate in warm acetone to give S31-4. Treatment with a Grignard reagent such as methylmagnesium bromide at –10 °C in a solvent such as DCM gives tertiary alcohol S31-5. Protodeiodination occurs on treatment with Zn metal and acetic acid in methanol to give S31-6. Palladium catalyzed borylation may be conducted in a solvent such as 1,4- dioxane by reaction with Bis(pinacolato)diboron, potassium acetate as base, and a palladium catalyst such as [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(I) to give S31-7. Reaction with Oxone gives rise to alcohol S31-8. Phenol alkylation occurs on treatment with an electrophile such as bis-tosylate S31-9 to give S31-10. Heating a mixture of S31-10, an amine nucleophile such as S31-11, and an inorganic base such as sodium bicarbonate in a solvent such as acetonitrile gives compounds of formula S31-12. Scheme 32

[0209] Compounds of formula S32-6 may be prepared according to Scheme 32. Heating a mixture of S32-1, 1,2-dibromoethane, and an inorganic base such as cesium carbonate gives S32-2. Heating a mixture of S32-2, an amine nucleophile such as S32-3, an inorganic base such as potassium bicarbonate, and potassium iodide in a solvent such as DMF gives compounds of formula S32-4. Compounds of formula S32-4 may be further elaborated by SNAr reaction withny-2734541207Docket No.: 79275-20025.40 an amine such as S32-5, a tertiary amine base such as triethylamine, in DMSO at 100 °C in a microwave reactor to give compounds of formula S32-6. Scheme 33S33-12

[0210] Compounds of formula S33-12 may be prepared according to Scheme 33. Reaction of diamine derivative S33-1 with a carboxylic acid such as S33-2 gives amide S33-3. Cyclization to benzimidazole S33-4 may be achieved by heating S33-3 in acetic acid. Treatment of S33-4 with an excess of 2-(Trimethylsilyl)ethoxymethyl chloride and sodium hydride in an aprotic solvent such as THF gives S33-5. Palladium catalyzed borylation may be conducted in a solvent such as 1,4-dioxane by reaction with diboron reagent S33-6, potassium acetate as base, and a palladium catalyst such as [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(I) to give S33-7. Treatment with Oxone in a mixed solvent such as THF and water gives S33-8.ny-2734541208Docket No.: 79275-20025.40 Alkylation with 1,2-dibromoethane in the presence of an inorganic base such as cesium carbonate gives S33-9. S33-9 may be coupled with amine S33-10 in hot acetonitrile in the presence of a base such as sodium bicarbonate to give S33-11. SEM-protecting group removal is achieved by treatment with a protic acid such as TFA, to give a benzimidazole which may then be converted to the free base by treatment with aqueous ammonia to deliver compounds of formula S33-12. Scheme 34S34-11

[0211] Compounds of formula S34-11 may be prepared according to Scheme 34. Reductive amination of an ortho-fluoro aldehyde such as S34-1 with an amine such as S34-2 with TFA and triethylsilane gives S34-3. SNAr reaction with an amine such as S34-4 occurs upon heating with DIEA in DMSO to give S34-5. Removal of the Boc-protecting group by treatment with a protic acid such as HCl in an aprotic solvent such as EtOAc gives amine S34-6, which can undergo conversion to the cyclic urea on treatment with CDI to give S34-7. Heating S34-7 in ethylene glycol, copper(I) iodide, and lithium tert-butoxide gives alcohol S34-8. Conversion of theny-2734541209Docket No.: 79275-20025.40 alcohol moiety to an alkyl bromide may be achieved by reaction with carbon tetrabromide and triphenyl phosphine in a solvent such as DCM to give S34-9. S34-9 may be coupled with amine S34-10 in hot acetonitrile in the presence of a base such as sodium bicarbonate to give compounds of formula S34-11. Scheme 35

[0212] Compounds of formula S35-9 may be prepared according to Scheme 35. SNAr reaction between S35-1 and amine S35-2 occurs upon heating with a tertiary amine base such as DIEA in DMSO solvent to give S35-3. Nitro group reduction by heating with iron and ammonium chloride in a mixed solvent such as ethanol and water gives S35-4. S35-4 is then converted to benzimidazole derivative S35-5 by heating in trimethyl orthoformate in the presence of p-toluene sulfonic acid. Heating S35-5 in ethylene glycol in the presence of copper (I) chloride and potassium carbonate gives the primary alcohol S35-6. Conversion to the alkyl iodide by treatment with iodine, imidazole, and triphenyl phosphine provides S35-7. S35-7 may beny-2734541210Docket No.: 79275-20025.40 coupled with amine S35-8 in hot acetonitrile in the presence of a base such as sodium bicarbonate to give compounds of formula S35-9. Scheme 36

[0213] Compounds of formula S36-13 may be prepared according to Scheme 36. Conversion of anilne S36-1 to corresponding sulfonyl chloride S36-2 occurs upon treatment with sodium nitrite, thionyl chloride, copper(I) chloride, and HCl. Reaction of S36-2 with aqueous ammonia provides sulfonamide S36-3. Reaction with N,N-dimethylformamide dimethyl acetal then generates N-sulfonylformamidine S36-4. Suzuki coupling with a vinyl boronate ester such as S36-5 gives enol ether S36-6. Treatment with HCl leads to hydrolysis of the formamidine and enol ether and cyclization to give S36-7. Hydrogenation of S36-7 with Pd / C as catalyst givesny-2734541211Docket No.: 79275-20025.40 S36-8. C-H oxidation of S36-8 with pinacol borane in the presence of catalyst Bis(1,5- cyclooctadiene)dimethoxydiiridium gives S36-9, which may undergo oxidation upon treatment with H2O2and potassium carbonate to give phenol derivative S36-10. S36-10 undergoes alkylation with 1,2-dibromoethane under conditions described above to deliver S36-11. Coupling of S36-11 with amine S36-12 under conditions described above gives compounds of formula S36-13. Scheme 37

[0214] Compounds of formula S37-12 may be prepared according to Scheme 37. SNAr reaction between S37-1 and amine S37-2 occurs upon heating with a tertiary amine base such as DIEA in solvent such as acetonitrile / THF to give S37-3. Nitro group reduction by heating with iron and ammonium chloride in a mixed solvent such as ethanol and water or by treatment with sodium dithionite in mixed solvent such as water and methanol followed by heating in aqueous HCl solution gives S37-4. Heating of S37-4 and an acid such as TsOH in an organic solvent such asny-2734541212Docket No.: 79275-20025.40 THF in the presence of an orthoester (S37-5) such as trimethyl orthoformate or 1,1,1- trimethoxyethane gives S37-6. Palladium catalyzed borylation may be conducted in a solvent such as 1,4-dioxane by reaction with diboron reagent S37-7, potassium acetate as base, and a palladium catalyst such as [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) to give S37-8. Treatment with Oxone in a mixed solvent such as THF and water gives S37-9. Alkylation with 1,2-dibromoethane in the presence of an inorganic base such as cesium carbonate gives S37-10. S37-10 may be coupled with amine S37-11 in hot acetonitrile in the presence of a base such as sodium bicarbonate to give compounds of formula S37-12. General Procedure for Intermediate A-1Step 1: 1-(4-methanesulfonylphenoxy)propan-2-one

[0215] A mixture of 4-methylsulfonylphenol (500 mg, 2.90 mmol), 1-chloropropan-2-one (268 mg, 2.90 mmol) and K2CO3(521 mg, 3.77 mmol) in DMF (10 mL) was stirred for 3 h. The reaction mixture was cooled to 0 °C and H2O (20 mL) was added. The biphasic mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with H2O (20 mL), brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give 1-(4- methylsulfonylphenoxy)propan-2-one (Intermediate A-1), which was taken to the next step without further purification. MS = 229.1 [M+H]+.

[0216] Intermediate A-2 in Table 2 was prepared according to procedures similar those described for Intermediate A-1 using the appropriate starting materials. General Procedure for Intermediate A-2 Table 2.ny-2734541213Docket No.: 79275-20025.40 General Procedure for Intermediate A-3Intermediate A-3 Step 1: 1-(2-bromoethoxy)-4-methanesulfonylbenzene:^

[0217] To a solution of 4-(methylsulfonyl)phenol (5.00 g, 29.0 mmol) in DMF (50 mL) were added Cs2CO3(18.9 g, 58.1 mmol) and 1,2-dibromoethane (11.0 mL, 145 mmol). The mixture was stirred at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was diluted with H2O (250 mL) and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 40 g cartridge, 0–60% EtOAc:petroleum ether). The crude product was triturated with MTBE (10 mL) to give 1-(2- bromoethoxy)-4-methanesulfonylbenzene (Intermediate A-3).1H NMR (400 MHz, DMSO-d6): δ 7.85 (d, J = 7.2 Hz, 2H), 7.19 (d, J = 6.8 Hz, 2H), 4.44 (t, J = 4.2 Hz, 2H), 3.84 (t, J = 4.2 Hz, 2H), 3.16 (s, 3H). MS = 279.0 / 281.0 [M+H]+.

[0218] The following intermediates in Table 3 were prepared according to procedures similar to steps described for Intermediate A-3 using the appropriate starting materials. General Procedure for Intermediates A-4 to A-8 & A-83 Table 3.ny-2734541214Docket No.: 79275-20025.40General Procedure for Intermediates A-9 and A-10Intermediate A-10 Step 1: 3-methanesulfonylpropyl methanesulfonate

[0219] To a 0 °C solution of 3-methanesulfonylpropan-1-ol (500 mg, 3.62 mmol) in DCM (5 mL) were added TEA (1.01 mL, 7.24 mmol) and methanesulfonic anhydride (945 mg, 5.43 mmol). The mixture was warmed to room temperature and stirred for 2 h. The reaction mixture was quenched with H2O (20 mL) and extracted with DCM (3 x 10 mL). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give 3- methanesulfonylpropyl methanesulfonate, which was used in the next step without further purification. Step 2: 4-[(3-methanesulfonylpropyl)sulfanyl]phenol

[0220] To a mixture of 4-sulfanylphenol (319 mg, 2.52 mmol) and 3-methanesulfonylpropyl methanesulfonate (390 mg, 1.80 mmol) in MeCN (10 mL) was added Cs2CO3(705 mg, 2.16 mmol). The mixture was stirred for 2 h, then was diluted with H2O (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (12 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 4 g cartridge, 0–60% EtOAc:petroleum ether) to give 4-[(3- methanesulfonylpropyl)sulfanyl]phenol. MS = 245.1 [M–H]–.ny-2734541215Docket No.: 79275-20025.40 Step 3: 4-(3-methanesulfonylpropanesulfonyl)phenol To a solution of 4-[(3-methanesulfonylpropyl)sulfanyl]phenol (370 mg, 1.50 mmol) in THF (3 mL) and H2O (3 mL) was added NaIO4(250 μL, 4.51 mmol). The mixture was stirred at 70 °C for 12 h. After cooling to room temperature, the reaction mixture was quenched with saturated aqueous Na2SO3(20 mL), then extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 4 g cartridge, 0– 60% EtOAc:petroleum ether) to give 4-(3-methanesulfonylpropanesulfonyl)phenol (Intermediate A-9). MS = 277.1 [M–H]–. Step 4: 1-(2-bromoethoxy)-4-(3-methanesulfonylpropanesulfonyl)benzene

[0221] To a solution of 4-(3-methanesulfonylpropanesulfonyl)phenol (Intermediate A-9) (300 mg, 1.08 mmol) in DMF (3 mL) were added K2CO3(223 mg, 1.62 mmol) and 1,2- dibromoethane (407 μL, 5.39 mmol). The mixture was stirred at 100 °C for 12 h. After cooling to room temperature, the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (8 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by preparative TLC (SiO2, 1:1 EtOAc:petroleum ether) to give 1-(2-bromoethoxy)-4-(3- methanesulfonylpropanesulfonyl)benzene (Intermediate A-10).1H NMR (400 MHz, DMSO- d6): δ 7.84 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 4.47 (t, J = 4.8 Hz, 2H), 3.86 (t, J = 5.2 Hz, 2H), 3.43 (t, J = 5.2 Hz, 2H), 3.22 (t, J = 7.6 Hz, 2H), 2.98 (s, 3H), 2.00–1.92 (m, 2H). General Procedure for Intermediate A-11Intermediate A-11 Step 1: 3,5-difluoro-4-methanesulfonylphenol

[0222] To a solution of 4-bromo-3,5-difluorophenol (1.00 g, 4.78 mmol) and MeSO2Na (4.88 g, 47.8 mmol) in DMSO (15 mL) were added CuI (91.1 mg, 0.478 mmol), DMEDA (84 mg, 0.956 mmol) and K3PO4(203 mg, 0.956 mmol). The mixture was stirred at 80 °C for 16 h. After cooling to room temperature, the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 0–50% EtOAc:petroleum ether) to giveny-2734541216Docket No.: 79275-20025.40 the crude product. The product was further purified by reverse phase preparative HPLC (Agela C18column, 5–35% Methanol: 0.04% HCl in H2O) to give 3,5-difluoro-4- methanesulfonylphenol (Intermediate A-11). MS = 207.1 [M–H]–. General Procedure for Intermediates A-12 and A-13Step 1: 4-bromo-3-(difluoromethyl)phenol

[0223] To a 0 °C solution of 2-bromo-5-hydroxybenzaldehyde (17.6 g, 87.5 mmol) in DCM (170 mL) was added DAST (14.1 g, 87.6 mmol) in one portion. The mixture was allowed to warm to room temperature and stirred for 3 h. The reaction mixture was cooled to 0 °C, quenched with saturated aqueous NaHCO3(150 mL), and extracted with DCM (2 x 100 mL). The combined organic layers were washed with brine (300 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 120 g cartridge, 8–15% EtOAc:petroleum ether) to give 4-bromo-3- (difluoromethyl)phenol. Step 2: 3-(difluoromethyl)-4-methanesulfonylphenol

[0224] A mixture of 4-bromo-3-(difluoromethyl)phenol (3.60 g, 16.1 mmol), sodium methanesulfinate (16.5 g, 161 mmol), NaOH (323 mg, 8.07 mmol), (2S)-pyrrolidine-2- carboxylic acid (929 mg, 8.07 mmol) and copper(I) iodide (3.07 g, 16.1 mmol) in DMSO (40 mL) was degassed and purged with N2(3x). The mixture was stirred at 100 °C for 48 h. The reaction mixture was poured into ice water (200 mL) and then extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with brine (2 x 300 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 80 g cartridge, 0–30% EtOAc:petroleum ether) to give 3- (difluoromethyl)-4-methanesulfonylphenol (Intermediate A-12).1H NMR (400 MHz, DMSO-ny-2734541217Docket No.: 79275-20025.40 d6): δ 11.04 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.67–7.40 (m, 1H), 7.20 (s, 1H), 7.11 (d, J = 4.2 Hz, 1H), 3.21 (s, 3H). Step 3: 4-(2-bromoethoxy)-2-(difluoromethyl)-1-methanesulfonylbenzene

[0225] To a solution of 3-(difluoromethyl)-4-methanesulfonylphenol (300 mg, 1.35 mmol) in 1, 2-dibromoethane (7.5 mL) was added Cs2CO3(1.32 g, 4.05 mmol). The mixture was stirred at 100 °C for 12 h. After cooling to room temperature, solids were removed by filtration and the filtrate was concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 20 g cartridge, 0–30% EtOAc:petroleum ether) to give 4-(2- bromoethoxy)-2-(difluoromethyl)-1-methanesulfonylbenzene (Intermediate A-13).1H NMR (400 MHz, DMSO-d6): δ 7.99 (d, J = 8.8 Hz, 1H), 7.74–7.55 (m, 1H), 7.47–7.32 (m, 2H), 4.56– 4.49 (m, 2H), 3.87–3.82 (m, 2H), 3.26 (s, 3H). General Procedure for Intermediate A-14Intermediate A-14 Step 1: 4-methoxy-N-(propan-2-yl)aniline

[0226] To a solution of 4-methoxyaniline (500 mg, 4.06 mmol) in DCM (10 mL) was added dropwise acetone (943 mg, 16.2 mmol) and AcOH (975 mg, 16.2 mmol). The mixture was stirred at room temperature for 1 h, and then NaBH(OAc)3(1.08 g, 5.08 mmol) was added. The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with H2O (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 0–30% EtOAc:petroleum ether) to give 4-methoxy-N-(propan-2-yl)aniline.1H NMR (400 MHz, DMSO- d6): δ 6.72–6.61 (m, 2H), 6.54–6.45 (m, 2H), 4.81 (s, 1H), 3.62 (s, 3H), 3.49–3.39 (m, 1H), 1.08 (d, J = 6.4 Hz, 6H). MS = 166.2 [M+H]+.ny-2734541218Docket No.: 79275-20025.40 Step 2: 2-chloro-N-(4-methoxyphenyl)-N-(propan-2-yl)acetamide

[0227] A mixture of 4-methoxy-N-(propan-2-yl)aniline (200 mg, 1.21 mmol), TEA (253 μL, 1.82 mmol) in DCM (3 mL) was degassed and purged with N2(3x). The mixture was cooled to 0 °C and 2-chloroacetyl chloride (273 mg, 2.42 mmol) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 12 h under N2atmosphere. The reaction mixture was quenched with H2O (15 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with saturated aqueous NaHCO3(20 ml) followed by brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 4 g cartridge, 0–40% EtOAc:petroleum ether) to give 2-chloro-N-(4-methoxyphenyl)-N-(propan-2-yl)acetamide. MS = 242.1 [M+H]+. Step 3: 5-hydroxy-1-(propan-2-yl)-2,3-dihydro-1H-indol-2-one

[0228] To 2-chloro-N-(4-methoxyphenyl)-N-(propan-2-yl)acetamide (1.00 g, 4.14 mmol) was slowly added aluminum chloride (2.21 g, 16.6 mmol). The mixture was stirred at 130 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with aqueous 1.0 M NaOH (20 mL), diluted with H2O (10 mL), and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 12 g cartridge, 0–40% EtOAc:petroleum ether) to give 5-hydroxy-1- (propan-2-yl)-2,3-dihydro-1H-indol-2-one. MS = 192.2 [M+H]+. Step 4: 5-(2-bromoethoxy)-1-(propan-2-yl)-2,3-dihydro-1H-indol-2-one

[0229] To a solution of 5-hydroxy-1-(propan-2-yl)-2,3-dihydro-1H-indol-2-one (500 mg, 2.61 mmol) in 1,2-dibromoethane (8 mL) was added Cs2CO3(2.56 g, 7.84 mmol). The mixture was stirred at 80 °C for 12 h. After cooling to room temperature, solids were removed by filtration and the filtrate was concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 12 g cartridge, 0–60% EtOAc:petroleum ether) to give 5-(2- bromoethoxy)-1-(propan-2-yl)-2,3-dihydro-1H-indol-2-one (Intermediate A-14). MS = 298.1 / 300.1 [M+H]+. General Procedure for Intermediates A-15 & A-16ny-2734541219Docket No.: 79275-20025.40Intermediate A-16 Step 1: 4-[(difluoromethyl)sulfanyl]phenol

[0230] To a solution of 4-sulfanylphenol (300 mg, 2.38 mmol) in DMF (4 mL) and H2O (1 mL) were added K2CO3 (1.97 g, 14.3 mmol) and 2-chloro-2,2-difluoro-acetic acid (302 μL, 3.57 mmol). The mixture was stirred at 120 °C for 15 h. After cooling to room temperature, the reaction mixture was quenched with H2O (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 0–30% EtOAc:petroleum ether) to give 4-[(difluoromethyl)sulfanyl]phenol. MS = 177.0 [M+H]+. Step 2: 4-difluoromethanesulfonylphenol

[0231] To a 0 °C solution of 4-[(difluoromethyl)sulfanyl]phenol (100 mg, 0.568 mmol) in THF (1 mL) and H2O (1 mL) was added NaIO4(94.4 μL, 1.70 mmol). The mixture was stirred at 70 °C for 15 h. After cooling to room temperature, the reaction mixture was quenched by the addition of saturated aqueous Na2SO3(20 mL), and then extracted with EtOAc (3 x 5 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 4 g cartridge, 0–30% EtOAc:petroleum ether) to give 4-difluoromethanesulfonylphenol (Intermediate A-15). MS = 207.0 [M–H]+. Step 3: 1-(2-bromoethoxy)-4-difluoromethanesulfonylbenzene

[0232] To a mixture of 4-(difluoromethylsulfonyl)phenol (500 mg, 2.40 mmol) and 1,2- dibromoethane (906 μL, 12.0 mmol) in DMF (5 mL) was added K2CO3(664 mg, 4.80 mmol). The mixture was stirred at 80 °C for 16 h. After cooling to room temperature, the reaction mixture was diluted with H2O (20 mL), and then extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 0–50% EtOAc:petroleum ether) to give 1-(2- bromoethoxy)-4-difluoromethanesulfonylbenzene (Intermediate A-16).1H NMR (400 MHz,ny-2734541220Docket No.: 79275-20025.40 DMSO-d6): δ 7.80 (d, J = 2.8 Hz, 2H), 7.21–7.04 (m, 3H), 4.95 (t, J = 7.2 Hz, 2H), 3.85 (t, J = 7.2 Hz, 2H). General Procedure for Intermediate A-17Intermediate A-17 Step 1: 4-methanesulfonyl-3-(trifluoromethyl)phenol

[0233] A mixture of 4-bromo-3-(trifluoromethyl)phenol (7.00 g, 29.1 mmol), sodium methanesulfinate (29.7 g, 290 mmol), CuI (2.77 g, 14.5 mmol), NaOH (581 mg, 14.5 mmol) and L-Proline (1.67 g, 14.5 mmol) in DMSO (100 mL) was degassed and purged with N2(3x). The mixture was stirred at 100 °C for 3 d under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with H2O (80 mL) and extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 80 g cartridge, 0–50% EtOAc:petroleum ether) to give 4- methanesulfonyl-3-(trifluoromethyl)phenol. MS = 239.1 [M–H]–. Step 2: 4-(2-bromoethoxy)-1-methanesulfonyl-2-(trifluoromethyl)benzene

[0234] To a solution of 4-methylsulfonyl-3-(trifluoromethyl)phenol (500 mg, 2.08 mmol) in DMF (5 mL) were added 1,2-dibromoethane (2.36 mL, 31.2 mmol) and K2CO3(575 mg, 4.16 mmol). The mixture was stirred at 80 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with H2O (8 mL) and extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with brine (2 x 10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 0–25% EtOAc:petroleum ether) to give 4-(2- bromoethoxy)-1-methanesulfonyl-2-(trifluoromethyl)benzene (Intermediate A-17). MS = 347.0 / 349.0 [M+H]+.

[0235] The following intermediates in Table 4 were prepared according to procedures similar those described for Intermediate A-17 using the appropriate starting materials. General Procedure for Intermediates A-18 to A-22 Table 4.ny-2734541221Docket No.: 79275-20025.40General Procedure for Intermediate A-23Step 1: 1-bromo-2-(difluoromethoxy)-4-methoxybenzeneny-2734541222Docket No.: 79275-20025.40

[0236] To a solution of 2-bromo-5-methoxyphenol (2.50 g, 12.3 mmol) in DMF (36 mL) and H2O (9 mL) were added K2CO3(10.2 g, 73.9 mmol) and sodium chlorodifluoroacetate (4.69 g, 30.8 mmol). The mixture was stirred at 120 °C for 15 h. After cooling to room temperature, the reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 40 g cartridge, 0–7% EtOAc:petroleum ether) to give 1-bromo-2- (difluoromethoxy)-4-methoxybenzene. Step 2: 2-(difluoromethoxy)-1-methanesulfonyl-4-methoxybenzene

[0237] A mixture of 1-bromo-2-(difluoromethoxy)-4-methoxybenzene (3.00 g, 11.9 mmol), sodium methanesulfinate (6.05 g, 59.3 mmol), L-Proline (409 mg, 3.56 mmol), sodium hydroxide (142 mg, 3.56 mmol) and copper (I) iodide (1.13 g, 5.93 mmol) in DMSO (30 mL) was degassed and purged with N2(3x). The mixture was stirred at 100 °C for 12 h under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with H2O (80 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine (40 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 80 g cartridge, 0–23% EtOAc:petroleum ether) to give 2-(difluoromethoxy)-1-methanesulfonyl-4-methoxybenzene. MS = 253.2 [M+H]+. Step 3: 3-(difluoromethoxy)-4-methanesulfonylphenol

[0238] A mixture of 2,2,4,6,6-pentamethylheptane-4-thiol (2.70 g, 13.3 mmol) and t-BuOK (1.56 g, 13.9 mmol) in DMF (14 mL) was degassed and purged with N2(3x). The mixture was cooled to 0 °C and a solution of 2-(difluoromethoxy)-1-methanesulfonyl-4-methoxybenzene (1.4 g, 5.55 mmol) in DMF (14 mL) was added dropwise. The resulting mixture was stirred at 50 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with H2O (50 mL) and extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 40 g cartridge, 0–33% EtOAc:petroleum ether) to give 3-(difluoromethoxy)-4-methanesulfonylphenol. MS = 239.2 [M+H]+. Step 4: 4-(2-bromoethoxy)-2-(difluoromethoxy)-1-methanesulfonylbenzene

[0239] To a mixture of 3-(difluoromethoxy)-4-methanesulfonylphenol (370 mg, 1.55 mmol) and 1,2-dibromoethane (3.00 mL, 39.7 mmol) in DMF (3 mL) was added Cs2CO3(1.01 g, 3.11ny-2734541223Docket No.: 79275-20025.40 mmol). After stirring at room temperature for 12 h, the mixture was diluted with H2O (15 mL) and extracted with DCM (3 x 10 mL). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Isco 4 g cartridge, 0–30% EtOAc:petroleum ether) to give 4-(2-bromoethoxy)-2-(difluoromethoxy)-1-methanesulfonylbenzene (Intermediate A-23). MS = 362.1 / 364.0 [M+NH4]+. General Procedure for Intermediate A-24Intermediate A-24 Step 1: methyl 2-[(4-fluorophenyl)sulfanyl]acetate

[0240] To a solution of 4-fluorobenzene-1-thiol (1.25 mL, 11.7 mmol) in DMF (15 mL) were added K2CO3(3.23 g, 23.4 mmol) and methyl 2-bromoacetate (1.33 mL, 14.0 mmol). The mixture was stirred at room temperature for 5 h. After cooling to 0 °C, the reaction mixture was quenched with H2O (15 mL) and extracted with EtOAc (2 x 15 mL). The combined organic layers were washed with brine (2 x 15 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 25 g cartridge, 1–20% EtOAc:petroleum ether) to give methyl 2-[(4-fluorophenyl)sulfanyl]acetate. MS = 201.0 [M+H]+. Step 2: methyl 2-(4-fluorobenzenesulfonyl)acetate

[0241] To a solution of methyl 2-[(4-fluorophenyl)sulfanyl]acetate (2.20 g, 11.0 mmol) in MeCN (30 mL) and H2O (3 mL) was added Oxone (8.11 g, 13.2 mmol). After stirring at roomny-2734541224Docket No.: 79275-20025.40 temperature for 16 h, the mixture cooled to 0 °C and quenched with saturated aqueous Na2S2O3(40 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine (2 x 20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 25 g cartridge, 15–45% EtOAc:petroleum ether) to give methyl 2-(4-fluorobenzenesulfonyl)acetate. MS = 233.0 [M+H]+. Step 3: methyl 1-(4-fluorobenzenesulfonyl)cyclopropane-1-carboxylate

[0242] To a solution of methyl 2-(4-fluorobenzenesulfonyl)acetate (1.10 g, 4.74 mmol) in DMF (10 mL) were added K2CO3(1.64 g, 11.8 mmol) and 1,2-dibromoethane (429 μL, 5.68 mmol). The mixture was stirred at 60 °C for 6 h. The reaction mixture was cooled to 0 °C, quenched with H2O (20 mL), and extracted with EtOAc (2 x 15 mL). The combined organic layers were washed with brine (2 x 15 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 15–45% EtOAc:petroleum ether) to give methyl 1-(4-fluorobenzenesulfonyl)cyclopropane-1- carboxylate. MS = 259.0 [M+H]+. Step 4: methyl 1-[4-(2-hydroxyethoxy)benzenesulfonyl]cyclopropane-1-carboxylate

[0243] To a solution of methyl 1-(4-fluorobenzenesulfonyl)cyclopropane-1-carboxylate (1.50 g, 5.81 mmol) in DMSO (15 mL) were added Cs2CO3(5.68 g, 17.4 mmol) and ethylene glycol (6.50 mL, 116 mmol). The mixture was stirred at 100 °C for 5 h. The hydrolysis product of the ester was detected. After cooling to room temperature, MeI (1.08 mL, 17.4 mmol) was added to the mixture. The reaction mixture was stirred at room temperature for 1 h and was then quenched with H2O (30 mL) and extracted with EtOAc (2 x 15 mL). The combined organic layers were washed with brine (2 x 15 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 45–80% EtOAc:petroleum ether) to give methyl 1-[4-(2- hydroxyethoxy)benzenesulfonyl]cyclopropane-1-carboxylate. MS = 301.1 [M+H]+. Step 5: methyl 1-{4-[2-(methanesulfonyloxy)ethoxy]benzenesulfonyl}cyclopropane-1- carboxylate

[0244] To a 0 °C solution of methyl 1-[4-(2-hydroxyethoxy)benzenesulfonyl]cyclopropane-1- carboxylate (570 mg, 1.90 mmol) in DCM (10 mL) were added TEA (528 μL, 3.80 mmol) and methylsulfonyl methanesulfonate (397 mg, 2.28 mmol). The mixture was stirred at 0 °C for 3 h, and then quenched with H2O (10 mL).4 M aqueous HCl (0.1 mL) was added, and the mixture was extracted with EtOAc (8 mL x 2). The combined organic layers were washed with brine (2 xny-2734541225Docket No.: 79275-20025.40 8 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give methyl 1-{4-[2- (methanesulfonyloxy)ethoxy]benzenesulfonyl}cyclopropane-1-carboxylate (Intermediate A- 24), which was used in the subsequent step without further purification. MS = 378.9 [M+H]+. General Procedure for Intermediates A-25 & A-85 OH HSIntermediate A-25 Step 1: 4-[(2-hydroxyethyl)sulfanyl]phenol

[0245] A solution of 4-bromophenol (10.0 g, 57.8 mmol), 2-sulfanylethanol (5.24 mL, 75.1 mmol), XantPhos (6.69 g, 11.6 mmol), Pd2(dba)3(5.29 g, 5.78 mmol) and DIEA (25.2 mL, 145 mmol) in 1,4-dioxane (10 mL) was degassed and purged with N2(3x). The mixture was stirred at 100 °C for 12 h under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with H2O (20 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 20 g cartridge, 0–50% EtOAc:petroleum ether) to give 4-[(2-hydroxyethyl)sulfanyl]phenol. Step 2: 4-(2-hydroxyethanesulfonyl)phenol

[0246] A solution of 4-[(2-hydroxyethyl)sulfanyl]phenol (4.80 g, 28.2 mmol), NaIO4(4.69 mL, 84.6 mmol) in THF (50 mL) and H2O (50 mL) was degassed and purged with N2(3x). The mixture was stirred at 70 °C for 12 h under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with saturated aqueous Na2S2O3(100 mL) and extracted with EtOAc (2 x 70 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give 4-(2-hydroxyethanesulfonyl)phenolny-2734541226Docket No.: 79275-20025.40 (Intermediate A-85), which was used in the subsequent step without further purification. MS = 203.0 [M+H]+. Step 3: 4-(2-chloroethanesulfonyl)phenol

[0247] To a 0 °C mixture of 4-(2-hydroxyethanesulfonyl)phenol (600 mg, 2.97 mmol) and pyridine (478 μL, 5.93 mmol) in DCM (6 mL) was added SOCl2(645 μL, 8.90 mmol). The mixture was stirred at 35 °C for 16 h. After cooling to room temperature, the reaction mixture was quenched with H2O (20 mL) and extracted with DCM (3 x 10 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by normal phase silica gel chromatography (Biotage 12 g cartridge, 0–100% EtOAc:petroleum ether) to give 4-(2-chloroethanesulfonyl)phenol. Step 4: 4-[2-(methylamino)ethanesulfonyl]phenol

[0248] A mixture of 4-(2-chloroethanesulfonyl)phenol (250 mg, 1.13 mmol), 2.0 M methylamine in MeOH (7.93 mL, 15.9 mmol), and KI (75 mg, 0.45 mmol) in THF (2 mL) was stirred at ...

Claims

Docket No.: 79275-20025.40 CLAIMS WHAT IS CLAIMED IS:

1. A method of treating diabetic retinopathy in a subject in need thereof, comprising administering to the subject an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

2. The method of claim 1, 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.

3. The method of claims 1 or 2, wherein the APOL1 inhibitor is a compound of formula (I):or a stereoisomer or a 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, C3-10cycloalkyl, or 3-15 membered heterocyclyl, whereinDocket No.: 79275-20025.40 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, and 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, 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 heterocycle, wherein the 3-10 membered heterocycle 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, whereinDocket No.: 79275-20025.40 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 -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 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 -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, andDocket No.: 79275-20025.40 the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and 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.

4. The method of any of claims 1-3, wherein a therapeutically effective amount of the APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient is administered.

5. The method of any of claims 1-4, wherein the administration comprises oral administration or intravitreal injection.

6. The method of claim 5, wherein the administration comprises oral administration.

7. The method of claim 5, wherein the administration comprises intravitreal injection.Docket No.: 79275-20025.40 8. The method of any of claims 1-7, 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 subject.

9. The method of any of claims 1-8, wherein the compound of formula (I), is a compound ofDocket No.: 79275-20025.40stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

10. A method of delaying the development of diabetic retinopathy in a subject in need thereof, comprising administering to the subject an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. The method of claim 10, 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.

12. The method of claims 10 or 11, wherein the APOL1 inhibitor is a compound of formula (I):or a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Docket No.: 79275-20025.40 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, 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, and 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, 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, whereinDocket No.: 79275-20025.40 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 heterocycle, wherein the 3-10 membered heterocycle 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 -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 whereinDocket No.: 79275-20025.40 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 -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and 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.

13. The method of any of claims 10-12, wherein a therapeutically effective amount of the APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or the pharmaceuticalDocket No.: 79275-20025.40 composition comprising an APOL1 inhibitor, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient is administered.

14. The method of any of claims 10-13, wherein the administration comprises oral administration or intravitreal injection.

15. The method of claim 13, wherein the administration comprises oral administration.

16. The method of claim 13, wherein the administration comprises intravitreal injection.

17. The method of any of claims 10-16, 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 subject.

18. The method of any of claims 10-17, wherein the compound of formula (I), is a compoundDocket No.: 79275-20025.40or a tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

19. A kit, comprising (i) an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and (ii) instructions for use in treating diabetic retinopathy in a subject in need thereof.

20. The kit of claim 19, 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.

21. The kit of claims 19 or 20, wherein the APOL1 inhibitor is a compound of formula (I):Docket No.: 79275-20025.40or a stereoisomer or a 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, 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, and 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 eitherDocket No.: 79275-20025.40 (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, 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 heterocycle, wherein the 3-10 membered heterocycle 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; orDocket No.: 79275-20025.40 (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 -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 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 -S(O)2-C1-6alkyl, the C3-10cycloalkyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and the 3-10 membered heterocyclyl of Rcis optionally substituted with one or more -OH or C1-6alkyl, and 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, whereinDocket No.: 79275-20025.40 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.

22. The kit of any of claims 19-21, wherein the kit comprises a therapeutically effective amount of the APOL1 inhibitor or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising an APOL1 inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

23. The kit of any of claims 19-22, wherein the administration comprises oral administration or intravitreal injection.

24. The kit of claim 23, wherein the administration comprises oral administration.

25. The kit of claim 23, wherein the administration comprises intravitreal injection.

26. The kit of any of claims 19-25, 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 subject.Docket No.: 79275-20025.40 27. The kit of any one of claims 21-26, wherein the compound of formula (I), is a compoundor a tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

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