Phosphonic acid and ester compounds and uses thereof

Abstract

Provided are compounds and compositions of Formula (I). In some embodiments, the compounds and compositions inhibit or degrade Pin1. Also provided are methods for treating diseases or conditions by inhibiting or degrading the activity of Pin1, comprising administering to a subject in need thereof the compounds and compositions herein.

Description

PHOSPHONIC ACID AND ESTER COMPOUNDS AND USES THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 711,465, filed October 24, 2024; U.S. Provisional Application No. 63 / 717,179, filed November 6, 2024; U.S. Provisional Application No. 63 / 744,054, filed January 10, 2025; U.S. Provisional Application No. 63 / 794,720, filed April 25, 2025; U.S. Provisional Application No.63 / 862,442, filed August 12, 2025; and U.S. Provisional Application No. 63 / 898,868, filed October 14, 2025; the contents of which are hereby incorporated by reference in their entirety for all purposes.FIELD OF INVENTION

[0002] The present invention relates to phosphonic acid and ester compounds and uses thereof. In some embodiments, the compounds inhibit or degrade Pinl. In some embodiments, the compounds are used, for example, in treating diseases associated with Pinl activity.BACKGROUND

[0003] Proline directed phosphorylation is critical in many biological processes such as proliferation, apoptosis, and the cell cycle (Ranganathan et al., Cell 1997, 6:875-866; Lu and Zhou / / . Rev. Mol. Cell. Biol. 2007, 8:904-906). Shifts or dysregulation of this event have been shown to have a significant effect in cancer. Many oncogenes and tumor suppressors are activated by this phosphorylation or they directly regulate proline directed phosphorylation. (Lu et al., Cell Res. 2014, 24:1033-1049, Lu et al., Nat. Chem Biol 2007 , 3:619-629). The Serine-Proline or Threonine-Proline (pSer / Thr-Pro) motifs can be rapidly isomerized (from cis to trans or trans to cis) by peptidyl-prolyl isomerase NIMA-interacting-1 (Pinl) (Lu and Zhou, Nat Rev Mol Cell Biol 2007, 8:904-916). This confirmation shift induces structural changes that effect the activation (Chen et al., Cell Death Dis 2018, 9:883), subcellular localization (Ryo et al., Nat Cell Biol 2001, 3:793-801), and stability of the targeted proteins (Lam et al., Mol Cancer 2008, 7:91; Liao et al., Oncogene 2009, 28:2436-2445; Lee et al., Nat Cell Biol 2009, 11 :97-105). Pinl is therefore an important mediator of proline-directed signaling networks, and frequently plays a role in cancer, through activating oncogenes and inactivating tumor suppressors (Chen et al, Cell Death Dis 2018, 9:883).

[0004] Several lines of evidence indicate that abnormal Pinl activation is a key driver of oncogenesis. Pinl has been reported to be overexpressed and / or overactivated in at least 38tumor types (Bao et al., Am J Pathol 2004, 164: 1727-1737), by mechanisms which include transcriptional activation (Rustighi et al., Nat Cell Biol 2009, 11 : 133-142; Ryo et al., Mol Cell Biol 2002, 22:5281-5295) and post-translational modifications (Lee eta / ., Mol Cell 2011, 42:147-159; Rangasamy et al., Proc Natl Acad Sci 2012, 109:8149-8154; Chen et al., Cancer Res 2013, 73: 3951-3962; Eckerdt et al., J Biol Chem 2005, 280:36575-36583).

[0005] Assessment of Pinl expression shows correlative effects to poor prognosis, disease progression, and / or increased risk of relapse in multiple cancer types (Gustavo et al, Cancer research 2003, 63:6244-6251, Wulf et al, The EMBO journal 2001, 20:3459-3472, Takeshi et al., Pathology research and practice 2005, 202:357-364). Additionally, Pinl expression in both cancer cells and cancer-associated fibroblasts is strongly correlated with poor survival in pancreatic cancer (Koikawa et. al. Cell 2021, 184: 4753-4771).

[0006] Pinl has been reported to sustain proliferative signaling in cancer cells by upregulating over 50 oncogenes or growth-promoting factors (Chen et al., Cell Death Dis 2018, 9:883), including NF-KB (Ryo et al., Mol Cell 2003, 12:1413-1426), c-Myc (Farrell et al., Mol Cell Biol 2013, 33:2930-2949), and Notchl (Rustighi et al., Nat Cell Biol 2009, 11 : 133-142), while suppressing over 20 tumor suppressors or growth -inhibiting factors, such as FOXOs (Brenkman et al., Cancer Res 2008, 68:7597-7605), Bcl2 (Basu et al., Neoplasia 2002, 4:218-227), and RARa (Gianni et al, Cancer Res 2009, 69:1016-1026).

[0007] Pinl depletion in human 3D pancreatic ductal adenocarcinoma (PDAC) co-cultures shows reduction in growth of the organoids (Koikawa et. al. Cell 2021, 184: 4753-4771). Furthermore, Pinl depletion was reported to inhibit tumorigenesis in mouse models derived by mutated p53 (Girardini et al., Cancer Cell 2011, 20:79-91), activated HER2 / RAS (Wulf et al., EMBO J 2004, 23:3397-3407), N-nitroso-N-methylrethane induced colon carcinoma (Li et. al. Cellular Signalling 2024, 115: 111041-111051), or constitutively expressed c-Myc (D1Artista et al., Oncotarget 2016, 7:21786-21798).

[0008] In addition, Pinl inhibition has been reported to sensitize cancer cells to chemotherapeutics (Gianni eta / ., Cancer Res 2009, 69:1016-1026; Zheng eta / ., Oncotarget 2017, 8:29771-29784; Sajadimajd & Yazdanparast, Apoptosis 2017, 22:135-144; Ding eta / ., Cancer Res 2008, 68:6109-6117) and to radiation (Liu et al., Nat Cell Biol 2019, 21:203-213), and block the tumorigenesis of cancer stem cells (Rustighi et al., Nat Cell Biol 2009, 11:133-142; Ding et al., Cancer Res 2008, 68:6109-6117; Min et al., Mol Cell 2012, 46:771-783), which are involved in the development of drug resistance (Dean et al., Nat Rev Cancer 2005, 5:275-284).

[0009] Hennig et al. (Biochemistry 1998, 37:5952-5960) described irreversible inhibition of several PPiases by juglone (5-hydroxy-l,4-naphthalenedione). Kim et al. (Mol Cancer Ther 2009, 8:2163-2171) reported that inhibition of Pinl - e.g., by juglone - reduces angiogenesis associated with growth factor release by tarn oxifen -resistant breast cancer. Campaner et al. (Nat Commun 2017 , 8:15772) reported that KPT-6566, a derivative ofjuglone, exhibited anti-cancer activity mediated by covalent inhibition of Pinl and release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage. Wei et al. (Nat Med 2015, 21 :457-466) reported that the anti-cancer activity of all-trans retinoic acid (ATRA) is mediated by inhibition of Pinl. Kozono et al. (Nat Commun 2018, 9:3069) reported that the anti-cancer activity of the combination of arsenic trioxide and ATRA is mediated by noncovalent binding of arsenic trioxide to Pinl and by enhancement by ATRA of arsenic tri oxide cellular uptake, as well as by inhibition of Pinl by ATRA. However, Pinl's potential as drug target remains elusive because available Pinl inhibitors lack the specificity and / or cell permeability to interrogate its pharmacological function in vivo (Lu & Hunter, Cell Res 2014, 24:1033-1049; Moore & Potter, Bioorganic Med Chem Lett 2013, 23:4283-4291; Fila et al., J Biol Chem 2008, 283:21714-21724).

[0010] These findings indicate that the inhibition of Pinl kinase activity and / or degradation of Pinl might have therapeutic potential across various diseases.SUMMARY OF THE INVENTION

[0011] In one aspect, provided is a compound of Formula (I):20 R1 / R0— o R33N PIx XR4p5 0* °or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Q, Ring 1, Ring 2, R1, R2, R3, R4, R5, and m are as detailed herein.

[0012] In some embodiments of the compound of Formula (I), Q is absent. In some embodiments, provided is a compound of Formula (II):or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1, Ring 2, R1, R2, R3, R4, R5, and m are as detailed herein.

[0013] In some embodiments of the compound of Formula (I), Q is Ring 3, which is as detailed herein. In some embodiments, provided is a compound of Formula (III):or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1, Ring 2, Ring 3, R1, R2, R3, R4, R5, and m are as detailed herein.

[0014] In some embodiments of the compound of Formula (I), Q is of Formula (i)wherein Ring A, X, Ring B, W, Ring C, Linker, Ring D, and Ring 4 are as detailed herein. In some embodiments, provided is a compound of Formula (IV):or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring A, X, Ring B, W, Ring C, Linker, Ring D, Ring 4, Ring 1, Ring 2, R1, R2, R3, R4, R5, and m are as detailed herein.

[0015] In another aspect, provided is a pharmaceutical composition comprising a compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (La), (I-b), (Lc), (Ld), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (Lm), (I-n), (Lo), (Lp), (I-q), (I-r), (I-s), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient. In someembodiments, provided is a pharmaceutical composition comprising an effective amount of a compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (Lm), (I-n), (Lo), (Lp), (I-q), (I-r), (I-s), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient. In some embodiments, provided is a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s), (Lt), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0016] In another aspect, provided is a method of making a compound of Formula (I), (II), (III), (III), or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s), (Lt), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (La), (Lb), (I-c), (I-d), (Le), (Lf), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0017] In another aspect, provided is a method of treating a disease or disorder associated with Pinl, comprising administering to a subject in need thereof (a) a compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (La), (Lb), (Lc), (I-d), (Le), (I-f), (Lg), (I-h), (I-j), (I-k), (Lm), (Ln), (Lo), (Lp), (Lq), (Lr), (I-s), (Lt), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q),(IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (Ln), (I-o), (I-p), (I-q), (I-r), (I-s), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0018] In another aspect, provided is a method of inhibiting Pinl in a cell, comprising exposing the cell to (a) a compound of Formula (I), (II), or (III), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s), or (I-t), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a compound of Formula (I), (II), or (III), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s), or (I-t), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0019] In another aspect, provided is a method of degrading Pinl in a cell, comprising exposing the cell to a compound of Formula (I) or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a compound of Formula (I) or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s),(I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (Lc), (I-d), (I-e), (Lf), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0020] In another aspect, provided is a method of treating a disease or disorder comprising modulating (e.g., reducing) the activity of Pinl, comprising administering to a subject in need thereof (a) an effective amount of the compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (Lq), (I-r), (Ls), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising an effective amount of the compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (Lq), (I-r), (Ls), (Lt), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient, to a subject in need thereof. In some embodiments, provided is a method of treating a disease or disorder comprising modulating (e.g., reducing) the activity of Pinl, comprising administering to a subject in need thereof (a) a therapeutically effective amount of the compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (La), (Lb), (Lc), (Ld), (I-e), (Lf), (I-g), (I-h), (I-j), (I-k), (I-m), (Ln), (I-o), (I-p), (Lq), (I-r), (Ls), (Lt), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a therapeutically effective amount of the compound of Formula (I), (II), (III), or (IV), or any related formula such as Formula (La), (Lb), (Lc), (I-d), (I-e), (Lf), (Lg), (Lh), (I-j), (Lk), (I-m), (Ln), (Lo), (Lp), (Lq), (I-r), (Ls), (Lt), (IV-a),(IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient, to a subject in need thereof. In some embodiments, the method comprises reducing the activity of Pinl. In some embodiments, the method comprises degrading Pinl. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0021] In another aspect, provided is a method of treating a disease or disorder comprising modulating (e.g., reducing) the activity of Pinl, comprising administering to a subject in need thereof (a) a compound of Formula (IV), or any related formula such as (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a compound of Formula (IV), or any related formula such as (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient, to a subject in need thereof. In some embodiments, the method comprises reducing the activity of Pinl. In some embodiments, the method comprises degrading Pinl. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0022] In another aspect, provided is a method of treating a disease or disorder comprising modulating (e.g., reducing) the activity of Pinl, comprising administering to a subject in need thereof (a) an effective amount of the compound of Formula (IV), or any related formula such as (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (IV), or any related formula such as (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient, to a subject in need thereof. In some embodiments, provided is a method of treating a disease or disorder comprising modulating (e.g., reducing) the activity of Pinl, comprising administering to a subject in need thereof (a) a therapeutically effective amount of the compound of Formula (IV), or any related formula such as (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (IV), or any related formula such as (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient, to a subject in need thereof. In some embodiments, the method comprises reducing the activity of Pinl. In some embodiments, the method comprises degrading Pinl. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0023] Any embodiments provided herein of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, apply where applicable to any other formula detailed herein, the same as if each and every embodiment were specifically and individually listed. Thus, it is understood and described that each embodiment provided herein of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, such as embodiments related to Ring 1, Ring 2, Ring 3, Ring 4, Ring A, Ring B, Ring C, Ring D, R1, R2, R3, R4, R5, m, Rla, Rlb, R2a, R2b, R3a, R3b, R4a, R4b, RB, Rc, RD, Rx, Ry, Rz, RLa, RLb, Q, X, W, Linker, p and n apply to any one of formulae (i), (II), (III), (IV), (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (Lo), (I-p), (I-q), (Lr), (Ls), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s),(IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), and (IV-ac), the same as if each and every embodiment were specifically and individually listed. It is also understood and described that all such embodiments may be used in any of the pharmaceutical compositions, methods, kits, uses, etc. comprising such compounds or other aspects detailed herein. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0024] As shown in working examples, compounds embraced by Formula (I) inhibit the activity or promote the degradation of Pinl. In some embodiments, compounds embraced by Formula (I) inhibit the activity of Pinl. In some embodiments, compounds embraced by Formula (I) promote the degradation of Pinl.

[0025] Without intending to be bound by any particular theory, the compounds of Formula (IV) and any related formula as applicable such as, e.g., (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac), are believed to cause degradation of Pinl by recruitment of cells’ Ubiquitin / Proteasome System, whose function is to routinely identify and remove damaged proteins, into close proximity with Pinl as a result of binding between Pinl and the targeting ligand. After destruction of a Pinl protein, the degrader is released and continues to be active. Thus, by engaging and exploiting the subject’s own natural protein disposal system, the compounds of the present invention may represent a potential improvement over current small molecule inhibitors of Pinl and may overcome one or more limitations regarding their use. Therefore, effective intracellular concentrations of the degraders may be significantly lower than for small molecule Pinl inhibitors. Also, although Pinl genetic knockdown or knockout can be used to reduce the cellular concentration or amount of these proteins, it may be preferable to post-translationally disrupt, degrade, or destabilize Pinl proteins. Targeting proteins directly, rather than via the DNA or mRNA molecules that encode them, is a more direct and rapid method for reducing the scaffolding function of Pinl proteins. Hence, degradation can allow some Pinl catalytic function to proceed while reducing the non-catalytic functions such as scaffolding between Pinl proteins and other cellular proteins and structures. Collectively, the present compounds may represent a set of new chemical tools for Pinl knockdown and may provide a potential treatment modality for Pinl -associated cancers and fibrotic diseases.Elevated hepatic and serum Pinl levels have been reported in non-alcoholic steatohepatitis (NASH) patients, and genetic or pharmacologic inhibition of Pinl reduces fibrosis in experimental liver, lung, renal, and cardiac models. The compounds may be used to treat solid cancers including refractory hormone receptor positive or triple negative breast cancer as described in, e.g., Ke et al., Nat Comm 2024, 15:3220, which is incorporated herein by reference in its entirety. Inhibitors and degraders of Pinl protein and methods for treating diseases or conditions, e.g. NASH / NAFLD, by modulating the level or activity of Pinl are also disclosed in Inoue et al., Cells 2019, 8:1545, herein incorporated by reference in its entirety.Brief Description of the Figures

[0026] FIG. 1A shows fold change in gene expression of myCAF genes between human primary colon cancer-associated fibroblasts (CAFs) non-targeting control (NTC) and Pinl knockdown (KD) cells. FIGS. IB - 1C show the protein quantification of connective tissue growth factor (CTGF) and hepatocyte growth factor (HGF) in CAFs with Pinl NTC or Pinl KD.

[0027] FIGS. 2A - 2B show Pinl and CTGF expression levels in human primary colon cancer-associated fibroblasts (CAFs). Cells were treated with Ex. B-4-1 for three days at different concentrations (i.e., 10 pM, 3 pM, and 1 pM). Pinl expression levels were assessed using high-content imaging techniques and CTGF was quantified via ELISA.

[0028] FIG. 3A shows Western blot analysis of HCT-116 colorectal cancer (CRC) 3D spheroids treated with various concentrations of Ex. B-4-1 [0 to 10 pM] over a 10-day period.FIG. 3B shows c-Myc activity in HCT-116 c-Myc reporter cell line after treated with varying concentrations of Ex. B-4-1 [0 to 10 pM], c-Myc reporter activity was measured using a luciferase assay

[0029] FIG. 4 shows the effect of Ex. B-5-1 on proliferation in multiple breast cancer cell lines.

[0030] FIG. 5 shows effect of PIN 1 degrader compounds on PIN1 expression levels in mouse PMBCs following IP administration of a single dose of PIN 1 degrader compounds.

[0031] FIG. 6 shows effect of PIN 1 degrader compounds on PIN1 expression levels in liver samples.

[0032] FIG. 7 shows that Pinl knockdown in human primary fibroblasts reduces stiff matrix + / - TGF-P induced myofibroblast differentiation.

[0033] FIG. 8 shows that Pint knockdown human primary fibroblasts are less responsive to TGF-P and secrete fewer pro-fibrotic mediators.

[0034] FIGS. 9A - 9B show that Compound 216 reduces early alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Measurements were taken at 42 days.

[0035] FIGS. 10A - 10D show that treatment with Compound 216 significantly reduced steatosis, ballooning degeneration, and the total NAFLD Activity Score (NAS) compared with vehicle controls, with a trend toward reduced lobular inflammation in male C57BL / 6J mice.

[0036] FIG. 11 shows that with a 4-week treatment duration, Compound 216 reduced hepatocellular injury and inflammation without substantially affecting established fibrosis.DETAILED DESCRIPTIONDefinitions

[0037] For use herein, unless clearly indicated otherwise, use of the terms “a”, “an” and the like refers to one or more.

[0038] Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. For example, “about X” includes and describes “X” per se. In some embodiments, the term “about,” when used in association with a measurement or to modify a parameter or a value or a range of values, refers to variations of that measurement, parameter, value, or range of values of ± 10%, ± 9%, ± 8%, ± 7%, ± 6%, ± 5%, ± 4%, ± 3%, ± 2%, or ± 1%. For example, in some embodiments, “about X” includes and describes X ± 10%, ± 9%, ± 8%, ± 7%, ± 6%, ± 5%, ± 4%, ± 3%, ± 2%, or ± 1% of X. In some embodiments, the term “about” refers to variations of ± 5%, ± 4%, ± 3%, ± 2%, or ± 1%. In some embodiments, the term “about” refers to variations of ± 2% or ± 1%. In some embodiments, the term “about” refers to variations of ± 2%. In some embodiments, the term “about” refers to variations of ± 1%.

[0039] “Alkyl” as used herein refers to and includes, unless otherwise stated, a saturated linear (z.e., unbranched) or branched univalent hydrocarbon chain or combination thereof, having the number of carbon atoms designated (z.e., Ci-io means one to ten carbon atoms). Particular alkyl groups are those having 1 to 10 carbon atoms (a “Ci-Cio alkyl”), having 6 to 10 carbon atoms (a “Ce-Cio alkyl”), having 1 to 6 carbon atoms (a “Ci-Ce alkyl”), having 2 to 6 carbon atoms (a “C2-C6 alkyl”), or having 1 to 4 carbon atoms (a “C1-C4 alkyl”). Particular C1-C4 alkyl groups include C1-C3 alkyl groups. Examples of alkyl groups include, but are notlimited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, secbutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, and the like.

[0040] “Alkylene” as used herein refers to the same residues as alkyl, but having bivalency. Particular alkylene groups are those having 1 to 10 carbon atoms (a “Ci-ioalkylene”), having 6 to 10 carbon atoms (a “Ce-ioalkylene”), having 1 to 6 carbon atoms (a “Ci-ealkylene”), 1 to 5 carbon atoms (a “Ci-salkylene”), 1 to 4 carbon atoms (a “Ci-4alkylene”) or 1 to 3 carbon atoms (a “C1-3 alkylene”). Examples of alkylene include, but are not limited to, groups such as methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), isopropylene (-CH2CH(CH3)-), butylene (-CEh CEh^CEh-), isobutylene (-CEECEhEEL^CEE-), pentylene (-CH2(CH2)3CH2-), hexylene (-CEh CEh^CEh-), heptylene (-CH2(CH2)sCH2-), octylene (-CH2(CH2)6CH2-), and the like.

[0041] "Carbocyclyl” as used herein refers to and includes, unless otherwise stated, saturated and partially unsaturated hydrocarbon structures, having the number of carbon atoms designated ( / .< ., C3-C10 means three to ten carbon atoms). Cycloalkyl can consist of one ring (e.g., cyclohexyl), or multiple rings (e.g., adamantyl). In polycyclic ring systems, one or more of the fused rings can be carbocyclyl or aryl (e.g., spiro[4.5]decanyl, or 1, 2,3,4-tetrahydronaphthalenyl), but excludes heterocyclyl or heteroaryl groups. A carbocyclyl comprising more than one ring may be fused, spiro or bridged, or combinations thereof.Particular carbocyclyl groups are those having from 3 to 12 annular carbon atoms (a “C3-12 carbocyclyl”), having 3 to 10 annular carbon atoms (a “C3-10 carbocyclyl”), having 3 to 8 annular carbon atoms (a "C3-C8 carbocyclyl"), having 3 to 6 annular carbon atoms (a “C3-C6 carbocyclyl”), or having from 3 to 4 annular carbon atoms (a "C3-C4 carbocyclyl"). A carbocyclyl group having more than one ring where at least one ring is aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position. In one variation, a carbocyclyl group having more than one ring where at least one ring is aromatic is connected to the parent structure at an aromatic ring position. In another variation, a carbocyclyl group having more than one ring where at least one ring is aromatic is connected to the parent structure at a non-aromatic ring position.

[0042] “Cycloalkyl” as used herein refers to and includes, unless otherwise stated, saturated cyclic hydrocarbon structures, having the number of carbon atoms designated (i.e., C3-C10 means three to ten carbon atoms). Cycloalkyl can consist of one ring (e.g., cyclohexyl), or multiple rings (e.g., adamantyl). In polycyclic ring systems, one or more of the fused rings can be cycloalkyl or aryl (e.g., spiro[4.5]decanyl, or 1,2,3,4-tetrahydronaphthalenyl), butexcludes heterocyclyl or heteroaryl groups. A cycloalkyl comprising more than one ring may be fused, spiro or bridged, or combinations thereof. Particular cycloalkyl groups are those having from 3 to 12 annular carbon atoms (a “C3-12 cycloalkyl”), having 3 to 10 annular carbon atoms (a “C3-10 cycloalkyl”), having 3 to 8 annular carbon atoms (a "C3-C8 cycloalkyl"), having 3 to 6 annular carbon atoms (a “C3-C6 cycloalkyl”), or having from 3 to 4 annular carbon atoms (a "C3-C4 cycloalkyl"). Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbomyl, and the like. A cycloalkyl group having more than one ring where at least one ring is aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position. In one variation, a cycloalkyl group having more than one ring where at least one ring is aromatic is connected to the parent structure at an aromatic ring position. In another variation, a cycloalkyl group having more than one ring where at least one ring is aromatic is connected to the parent structure at a non-aromatic ring position.

[0043] “Aryl” or “Ar” as used herein refers to an unsaturated aromatic carbocyclic group having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) which condensed rings must be aromatic. Particular aryl groups are those having from 6 to 14 annular carbon atoms (a “Ce-Cu aryl”).

[0044] “Heteroaryl” as used herein refers to an unsaturated aromatic cyclic group having from 1 to 14 annular carbon atoms and at least one annular heteroatom, including but not limited to heteroatoms such as nitrogen, oxygen and sulfur. A heteroaryl group may have a single ring (e.g., pyridyl, furyl) or multiple condensed rings (e.g., indolizinyl, benzothienyl) which condensed rings must be aromatic. Particular heteroaryl groups are 5 to 14-membered rings having 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 5 to 10-membered rings having 1 to 8 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, or 5, 6 or 7-membered rings having 1 to 5 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In one variation, particular heteroaryl groups are monocyclic aromatic 5-, 6- or 7-membered rings having from 1 to 6 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In another variation, particular heteroaryl groups are polycyclic aromatic rings having from 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. A heteroaryl group may be connected to the parent structure at a ring carbon atom or a ring heteroatom.

[0045] “Heterocycle”, “heterocyclic”, or “heterocyclyl” as used herein refers to a saturated or partially unsaturated non-aromatic cyclic group having a single ring or multiple condensed rings, and having from 1 to 14 annular carbon atoms and from 1 to 6 annular heteroatoms, such as nitrogen, sulfur or oxygen, and the like. A heterocycle comprising more than one ring may be fused, bridged or spiro, or any combination thereof. In fused ring systems, one or more of the fused rings can be cycloalkyl, aryl, or heteroaryl groups. The heterocyclyl group may be optionally substituted independently with one or more substituents described herein. Particular heterocyclyl groups are 3 to 14-membered rings having 1 to 13 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 12-membered rings having 1 to 11 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 10-membered rings having 1 to 9 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 8-membered rings having 1 to 7 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, or 3 to 6-membered rings having 1 to 5 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In one variation, heterocyclyl includes monocyclic 3-, 4-, 5-, 6- or 7-membered rings having from 1 to 2, 1 to 3, 1 to 4, 1 to 5, or 1 to 6 annular carbon atoms and 1 to 2, 1 to 3, or 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In another variation, heterocyclyl includes polycyclic non-aromatic rings having from 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. A heterocyclyl group having more than one ring where at least one ring is aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position. In one variation, a heterocyclyl group having more than one ring where at least one ring is aromatic is connected to the parent structure at an aromatic ring position. In another variation, a heterocyclyl group having more than one ring where at least one ring is aromatic is connected to the parent structure at a non-aromatic ring position.

[0046] “Halo” or “halogen” refers to elements of the Group 7 of the periodic table.Preferred halo groups include fluorine, chlorine, bromine and iodine. Where a residue is substituted with more than one halogen, it may be referred to by using a prefix corresponding to the number of halogen moi eties attached, e.g., dihaloaryl, dihaloalkyl, trihaloaryl etc. refer to aryl and alkyl substituted with two (“di”) or three (“tri”) halo groups, which may be but are not necessarily the same halogen; thus 4-chl oro-3 -fluorophenyl is within the scope ofdihaloaryl. An alkyl group in which each hydrogen is replaced with a halo group is referred to as a “perhaloalkyl.” A preferred perhaloalkyl group is trifluoromethyl (-CF3). Similarly, “perhaloalkoxy” refers to an alkoxy group in which a halogen takes the place of each H in the hydrocarbon making up the alkyl moiety of the alkoxy group. An example of a perhaloalkoxy group is trifluoromethoxy (-OCF3).

[0047] “Carbonyl” refers to the group C=O.

[0048] “ Oxo” refers to the moiety =0.

[0049] “Optionally substituted” unless otherwise specified means that a group may be unsubstituted or substituted with one or more (e.g., 1, 2, 3, 4 or 5) of the substituents listed for that group in which the substituents may be the same of different. In one embodiment, an optionally substituted group has one substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In another embodiment, an optionally substituted group has four substituents. In some embodiments, an optionally substituted group has 1 to 2, 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, or 2 to 5 substituents. In one embodiment, an optionally substituted group is unsubstituted.

[0050] It is understood that aspects and embodiments described herein as “comprising” include “consisting of’ and “consisting essentially of’ embodiments.

[0051] 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. 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.

[0052] 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.

[0053] The compounds of the present disclosure, or their pharmaceutically acceptable salts, may include asymmetric centers or stereocenters, and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms. The stereocenters in the compounds may be defined, in terms of absolute stereochemistry, e.g., as (R)- or (5)- (or as (D)- or (L)- for amino acids). Unless otherwise indicated, the present disclosure is intended to include all such possible isomers, as well as their racemic and optically pure forms and mixtures thereof in any ratio.

[0054] Optically active (+) and (-), (R)- and (5 -, 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 stereoisomers include chiral synthesis from a suitable optically pure precursor or the resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC), and 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.

[0055] The present disclosure contemplates various stereoisomers, or mixtures thereof (e.g., racemic mixtures), 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. Where enantiomeric and / or diastereomeric forms can exist for a given structure, flat bonds or wedge / hash bonds with the “and#” or “&#” label (e.g., R andl, S andl, andl, and2, and3, R &1, S &1, &1, &2, or &3,) indicate that both stereoisomeric forms are presentat the particular stereocenters (for wedge / hash groups with the “and#” or “&#” label, configuration both as depicted and the opposite configuration as / to what is depicted arepresent), e.g. ,. Where enantiomeric and / or diastereomeric forms exist of a given structure, wedged or hashed bonds with “R”, “S”, or “abs” indicate the composition is made up of at least 90% by weight of a single enantiomer or diastereomer ,F / / with known absolute stereochemistry, e.g., o OH . Where the composition is made up of at least 90% by weight of a single enantiomer or diastereomer with unknown absolute stereochemistry then “or#” is used.

[0056] For enhanced stereochemistry labels there are three types of stereo groups: “abs” indicates that the absolute stereochemistry of the labeled stereo group is known, “and” indicates that the stereocenter represents a mixture of the stereoisomer as drawn and its mirror image, and “or” indicates that the stereocenter represents either the stereoisomer as drawn or its mirror image but the stereochemical assignment is unknown. If # in the label is the same then the bonds are in relation to each other and have a relative stereochemicalconfiguration, e.g. . If # in the label is different, then the bonds are independent of one another and do not have relative stereochemistry, e.g,

[0057] In some instances, diastereomeric mixtures are designated using “r”, “s” “RS”, “SR”, rac-, and / or “and#” configurations. In such instances, relative stereochemistry is designated by lowercase (“r” or “s”), and absolute stereochemistry is designated by uppercase (“R” or “S”). For a compound where “and#” is notated in the structure then the naming convention can be described as follows: If the compound contains an enhanced stereochemistry label “and#” without the presence of a “or#” and / or “abs” label then rac- will OHO=P-OHbe used, e.g., [rac-(R)-( 1 , 1 -difluoro-3 -(3 -fluorophenyl)-2-( 1 -methyl -4-phenyl- lH-imidazole-2-carboxamido)propyl)phosphonic acid]. If the compound contains an enhanced stereochemistry label “and#” with the presence of a “or#” and / or “abs” label then the “and#” stereocenter is denoted with “RS” or “SR” e.g.,[((R)-2-(5-(l-(5-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid] .

[0058] The term “disease” as used herein is regarded as a state of health of a subject, wherein the subject cannot maintain homeostasis, and / or wherein, if the disease is not ameliorated, then the subject's health further deteriorates. In contrast, a "disorder" in a subject is a state of health in which the subject is able to maintain homeostasis, but the subject’s health is less favorable than it in the absence of the disorder. A disorder does not necessarily cause a further decrease in the subject’s health, when left untreated.

[0059] The term “subject” as used herein includes mammals prone to or suffering from the indicated disease or disorder e.g., a human or a non-human mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a companion animal such as dogs and cats; in some embodiments, the subject is a livestock animal such as cows, horses, sheep,goats, and pigs; in some embodiments, the subject may be other domesticated and wild animals. A subject “in need of’ treatment according to the present invention may be “suffering from or suspected of suffering from” a specific disease or disorder; may have been positively diagnosed with the disease or disorder; or otherwise presents with a sufficient number of risk factors or combination of symptoms such that a medical professional could diagnose the subject with the disease or disorder or suspect that the subject was suffering from the disease or disorder.

[0060] As used herein, the term, "therapeutically effective amount" is an amount that is effective in yielding the desired therapeutic response in a particular subject in need thereof. Therefore, the term "therapeutically effective amount" includes the amount of a compound, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, that when administered, induces an improvement in the disease or disorder to be treated, or is sufficient to prevent or slow development or progression of the disease or disorder, or alleviate to some extent one or more of the symptoms of the disease or disorder being treated in a subject, or kills or inhibits the growth of diseased cells (e.g., cancer cells, or autophagy-dependent disease cells), or reduces the amount of at Pinl in diseased cells.

[0061] “ 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).

[0062] As used herein, the term “cell proliferative disease or disorder” refers to a condition characterized by dysregulated or abnormal cell growth, or both, including noncancerous conditions such as neoplasms, precancerous conditions, benign tumors, and cancer.

[0063] As used herein, “cell proliferative diseases or disorders of the hematological system” include lymphoma, leukemia, myeloid neoplasms, mast cell neoplasms, myelodysplasia, benign monoclonal gammopathy, lymphomatoid papulosis, polycythemia vera, chronic myelocytic leukemia, agnogenic myeloid metaplasia, and essential thrombocythemia. Representative examples of hematologic cancers may thus includemultiple myeloma, lymphoma (including T-cell lymphoma, Hodgkin’s lymphoma, nonHodgkin’s lymphoma (diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and ALK+ anaplastic large cell lymphoma (e.g., B-cell nonHodgkin’s lymphoma selected from diffuse large B-cell lymphoma (e.g., germinal center B-cell-like diffuse large B-cell lymphoma or activated B-cell-like diffuse large B-cell lymphoma), Burkitt’s lymphoma / leukemia, mantle cell lymphoma, mediastinal (thymic) large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma / Waldenstrom macroglobulinemia, metastatic pancreatic adenocarcinoma, refractory B-cell non-Hodgkin’s lymphoma, and relapsed B-cell non-Hodgkin’s lymphoma, childhood lymphomas, and lymphomas of lymphocytic and cutaneous origin, e.g., small lymphocytic lymphoma, leukemia, including childhood leukemia, hairy-cell leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloid leukemia (e.g., acute monocytic leukemia), chronic lymphocytic leukemia, small lymphocytic leukemia, chronic myelocytic leukemia, chronic myelogenous leukemia, and mast cell leukemia, myeloid neoplasms and mast cell neoplasms.

[0064] As used herein, “cell proliferative diseases or disorders of the liver” include all forms of cell proliferative disorders affecting the liver. Cell proliferative disorders of the liver may include liver cancer (e.g., hepatocellular carcinoma, intrahepatic cholangiocarcinoma and hepatoblastoma), a precancer or precancerous condition of the liver, benign growths or lesions of the liver, and malignant growths or lesions of the liver, and metastatic lesions in tissue and organs in the body other than the liver. Cell proliferative disorders of the liver may include hyperplasia, metaplasia, and dysplasia of the liver.

[0065] As used herein, “cell proliferative diseases or disorders of the brain” include all forms of cell proliferative disorders affecting the brain. Cell proliferative disorders of the brain may include brain cancer (e.g., gliomas, glioblastomas, meningiomas, pituitary adenomas, vestibular schwannomas, and primitive neuroectodermal tumors (medulloblastomas)), a precancer or precancerous condition of the brain, benign growths or lesions of the brain, and malignant growths or lesions of the brain, and metastatic lesions in tissue and organs in the body other than the brain. Cell proliferative disorders of the brain may include hyperplasia, metaplasia, and dysplasia of the brain.

[0066] As used herein, “cell proliferative diseases or disorders of the lung” include all forms of cell proliferative disorders affecting lung cells. Cell proliferative disorders of the lung include lung cancer, precancer and precancerous conditions of the lung, benign growthsor lesions of the lung, hyperplasia, metaplasia, and dysplasia of the lung, and metastatic lesions in the tissue and organs in the body other than the lung. Lung cancer includes all forms of cancer of the lung, e.g., malignant lung neoplasms, carcinoma in situ typical carcinoid tumors, and atypical carcinoid tumors. Lung cancer includes small cell lung cancer (“SLCL”), non-small cell lung cancer (“NSCLC”), adenocarcinoma, small cell carcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma. Lung cancer can include “scar carcinoma”, bronchoalveolar carcinoma, giant cell carcinoma, spindle cell carcinoma, and large cell neuroendocrine carcinoma. Lung cancer also includes lung neoplasms having histologic and ultrastructural heterogeneity (e.g., mixed cell types). In some embodiments, a compound treats non-metastatic or metastatic lung cancer (e.g., NSCLC, ALK-positive NSCLC, NSCLC harboring ROS1 rearrangement, lung adenocarcinoma, and squamous cell lung carcinoma).

[0067] As used herein, “cell proliferative diseases or disorders of the colon” include all forms of cell proliferative disorders affecting colon cells, including colon cancer, a precancer or precancerous conditions of the colon, adenomatous polyps of the colon and metachronous lesions of the colon. Colon cancer includes sporadic and hereditary colon cancer, malignant colon neoplasms, carcinoma in situ, typical carcinoid tumors, and atypical carcinoid tumors, adenocarcinoma, squamous cell carcinoma, and squamous cell carcinoma. Colon cancer can be associated with a hereditary syndrome such as hereditary nonpolyposis colorectal cancer, familiar adenomatous polyposis, MYH associated polyposis, Gardner’s syndrome, Peutz-Jeghers syndrome, Turcot’s syndrome and juvenile polyposis. Cell proliferative disorders of the colon may also be characterized by hyperplasia, metaplasia, or dysplasia of the colon.

[0068] As used herein, “cell proliferative diseases or disorders of the pancreas” include all forms of cell proliferative disorders affecting pancreatic cells. Cell proliferative disorders of the pancreas may include pancreatic cancer, a precancer or precancerous condition of the pancreas, hyperplasia of the pancreas, dysplasia of the pancreas, benign growths or lesions of the pancreas, and malignant growths or lesions of the pancreas, and metastatic lesions in tissue and organs in the body other than the pancreas. Pancreatic cancer includes all forms of cancer of the pancreas, including ductal adenocarcinoma, adenosquamous carcinoma, pleomorphic giant cell carcinoma, mucinous adenocarcinoma, osteoclast-like giant cell carcinoma, mucinous cystadenocarcinoma, acinar carcinoma, unclassified large cell carcinoma, small cell carcinoma, pancreatoblastoma, papillary neoplasm, mucinouscystadenoma, papillary cystic neoplasm, and serous cystadenoma, and pancreatic neoplasms having histologic and ultrastructural heterogeneity (e.g., mixed cell).

[0069] As used herein, “cell proliferative diseases or disorders of the prostate” include all forms of cell proliferative disorders affecting the prostate. Cell proliferative disorders of the prostate may include prostate cancer, a precancer or precancerous condition of the prostate, benign growths or lesions of the prostate, and malignant growths or lesions of the prostate, and metastatic lesions in tissue and organs in the body other than the prostate. Cell proliferative disorders of the prostate may include hyperplasia, metaplasia, and dysplasia of the prostate.

[0070] As used herein, “cell proliferative diseases or disorders of the ovary” include all forms of cell proliferative disorders affecting cells of the ovary. Cell proliferative disorders of the ovary may include a precancer or precancerous condition of the ovary, benign growths or lesions of the ovary, ovarian cancer, and metastatic lesions in tissue and organs in the body other than the ovary. Cell proliferative disorders of the ovary may include hyperplasia, metaplasia, and dysplasia of the ovary.

[0071] As used herein, “cell proliferative diseases or disorders of the breast” include all forms of cell proliferative disorders affecting breast cells. Cell proliferative disorders of the breast may include breast cancer, a precancer or precancerous condition of the breast, benign growths or lesions of the breast, and metastatic lesions in tissue and organs in the body other than the breast. Cell proliferative disorders of the breast may include hyperplasia, metaplasia, and dysplasia of the breast. Representative examples of cell proliferative diseases or disorders of the breast may thus include ductal carcinoma in situ, invasive breast cancer, triple negative breast cancer, inflammatory breast cancer, Paget disease of the breast, angiosarcoma, phyllodes tumor, estrogen receptor-positive (ER+) breast cancer, and HER2-positive (HER2+) breast cancer.

[0072] As used herein, “cell proliferative diseases or disorders of the skin” include all forms of cell proliferative disorders affecting skin cells. Cell proliferative disorders of the skin may include a precancer or precancerous condition of the skin, benign growths or lesions of the skin, melanoma, malignant melanoma or other malignant growths or lesions of the skin, and metastatic lesions in tissue and organs in the body other than the skin. Cell proliferative disorders of the skin may include hyperplasia, metaplasia, and dysplasia of the skin.

[0073] As used herein, “cell proliferative diseases or disorders of the endometrium” include all forms of cell proliferative disorders affecting cells of the endometrium. Cell proliferative disorders of the endometrium may include a precancer or precancerous condition of the endometrium, benign growths or lesions of the endometrium, endometrial cancer, and metastatic lesions in tissue and organs in the body other than the endometrium. Cell proliferative disorders of the endometrium may include hyperplasia, metaplasia, and dysplasia of the endometrium.

[0074] In some embodiments, the cancer is a hematological cancer e.g., leukemia, lymphoma or multiple myeloma.Compounds of Formula (I)

[0075] In one aspect, provided is a compound of Formula (I):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Q is absent or is Ring 3,wherein Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8- membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12- membered heterocyclyl optionally substituted with one or more R3b;or Q is of formula (i):wherein:Ring A is selected from the group consisting of:each of which is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo;X is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, -or -N(Ry)C(0)-;Ring B is selected from the group consisting of:oeach of which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X;W is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, or -N(Ry)C(0)-;Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl optionally substituted with one or more Rc, 3- to 8-membered cycloalkyl optionally substituted with one or more Rc, 6- to 10-membered aryl optionally substituted with one or more RCa, or 5- to 10-membered heteroaryl optionally substituted with one or more RCa;Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(O)N(Ry)-, -N(Ry)C(O)-, C(O)O-, -OC(O), Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-0-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, C(0)0-Ci-ioalkylene, Ci-ioalkyleneC(0)0-, C(0)0-Ci-ioalkyleneC(0)0-, Ci- ioalkyleneC(0)0-Ci-ioalkylene, -OC(0)Ci-ioalkylene, Ci-ioalkylene-OC(O), -OC(0)Ci-ioalkylene-OC(0), Ci-ioalkylene-OC(0)Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-© i-walkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, -(6- to 10-membered arylene)-O-, -O-(6-to 10-membered arylene)-, -(6- to 10-membered arylene)-O-(6- to 10-membered arylene)-, -O-(6- to 10-membered arylene)-O-, -(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-O-(5- to 10-membered heteroarylene)-, -O-(5- to 10-membered heteroarylene)-O-, -(4-to 12-membered heterocyclylene)-©-, -O-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-O-(4- to 12-membered heterocyclylene)-, -O-(4- to12-membered heterocyclylene)-O-, -(3- to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-O-(3- to 8-membered cycloalkylene)-, -O-(3- to 8-membered cycloalkylene)-O-, -(6- to 10-membered arylene)-C(O)-, -C(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)-(6- to 10-membered arylene)-, -C(O)-(6- to 10-membered arylene)-C(O)-, -(5- to 10-membered heteroarylene)-C(O)-, -C(O)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)-(5- to 10-membered heteroarylene)-, -C(O)-(5- to 10-membered heteroarylene)-C(O)-, -(4- to 12-membered heterocyclylene)-C(O)-, -C(O)-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-C(O)-(4- to 12-membered heterocyclylene)-, -C(O)-(4- to 12-membered heterocyclylene)-C(O)-, -(3- to 8-membered cycloalkylene)-C(O)-, -C(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)-(3- to 8-membered cycloalkylene)-, -C(O)-(3- to 8-membered cycloalkylene)-C(O)-, -(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)-(6- to 10-membered arylene)-, -N(Ry)-(6- to 10-membered arylene)-N(Ry)-, -(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)-(5- to 10-membered heteroarylene)-, -N(Ry)-(5- to 10-membered heteroarylene)-N(Ry)-, -(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)-(4- to 12-membered heterocyclylene)-, -N(Ry)-(4- to 12-membered heterocyclylene)-N(Ry)-, -(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)-(3- to 8-membered cycloalkylene)-, -N(Ry)-(3- to 8-membered cycloalkylene)-N(Ry)-, -(6- to 10-membered arylene)-C(O)N(Ry)-, -C(0)N(Ry)-(6- to 10-membered arylene)-, -(6-to 10-membered arylene)-C(0)N(Ry)-(6- to 10-membered arylene)-, -C(0)N(Ry)-(6-to 10-membered arylene)-C(O)N(Ry)-, -(5- to 10-membered heteroarylene)-C(0)N(Ry)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-(5- to 10-membered heteroarylene)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -(4- to 12-membered heterocyclylene)-C(0)N(Ry)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)N(Ry)-(4- to 12-membered heterocyclylene)-, -C(0)N(Ry)-(4-to 12-membered heterocyclylene)-C(O)N(Ry)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-(3- to 8-membered cycloalkylene)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -(6- to 10-membered arylene)-N(Ry)C(O)-, -N(Ry)C(0)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)C(O)-(6- to 10-membered arylene)-, -N(Ry)C(0)-(6- to 10-membered arylene)-N(Ry)C(O)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-(5- to 10-membered heteroarylene)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-(4- to 12-membered heterocyclylene)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-N(Ry)C(0)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-(3- to 8-membered cycloalkylene)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-N(Ry)C(0)-, -(6- to 10-membered arylene)-C(O)O-, -C(O)O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)O-(6- to 10-membered arylene)-, -C(O)O-(6- to 10-membered arylene)-C(O)O-, -(5- to 10-membered heteroarylene)-C(O)O-, -C(O)O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)O-(5- to 10-membered heteroarylene)-, -C(O)O-(5- to 10-membered heteroarylene)-C(O)O-, -(4- to 12-membered heterocyclylene)-C(O)O-, -C(O)O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)O-(4- to 12-membered heterocyclylene)-, -C(O)O-(4- to 12-membered heterocyclylene)-C(O)O-, -(3- to 8-membered cycloalkylene)-C(O)O-, -C(O)O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)O-(3- to 8-membered cycloalkylene)-, -C(O)O-(3- to 8-membered cycloalkylene)-C(O)O-, -(6-to 10-membered arylene)-OC(O)-, -OC(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-OC(O)-(6- to 10-membered arylene)-, -OC(O)-(6- to 10-membered arylene)-OC(O)-, -(5- to 10-membered heteroarylene)-OC(O)-, -OC(O)-(5-to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-OC(O)-(5- to 10-membered heteroarylene)-, -OC(O)-(5- to 10-membered heteroarylene)-OC(O)-, -(4- to 12-membered heterocyclylene)-OC(O)-, -OC(O)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-OC(O)-(4- to 12-membered heterocyclylene)-, -OC(O)-(4- to 12-membered heterocyclylene)-OC(O)-, -(3- to 8-membered cycloalkylene)-OC(O)-, -OC(O)-(3- to 8-membered cycloalkylene)-, -(3-to 8-membered cycloalkylene)-OC(O)-(3- to 8-membered cycloalkylene)-, -OC(O)-(3- to 8-membered cycloalkylene)-OC(O)-, Ci-ioalkylene-(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)N(Ry)-, C(0)N(Ry)-(6-to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)C(0), -N(Ry)C(0)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6-to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroaryl ene)C(O), C(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)C(O), -N(Ry)C(0)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-O-, -O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4-to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)C(0), -N(Ry)C(0)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8- membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci- ioalkylene-(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8- membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)C(O), -N(Ry)C(0)(3- to 8-membered cycloalkylene)-Ci- walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8- membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene;wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8- membered cycloalkylene of Linker are independently optionally substituted with RLb; andwherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc;Ring D is optional, and when present is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD; andRing 4 is phenyl optionally substituted with one or more R4a, 5- to 10- membered heteroaryl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b;wherein Ring 4 and Ring 1 are connected via a bond, -N(Ry)-, -O-, - C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, -OC(O), or Ci-ioalkylene optionally substituted with one or more oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Cl.4alkylene-N(Rv)C(O)Cl.4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl,S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rlb, R2b, R3b, and R4bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl; andeach Rc, RD, RLb, and RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each RCais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;wherein Q is Ring 3 or of formula (i) when R1is H, R2is H, and Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0076] In one aspect, provided is a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Q is absent or is Ring 3,wherein Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8- membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12- membered heterocyclyl optionally substituted with one or more R3b;or Q is of formula (i):wherein:Ring A is selected from the group consisting of:each of which is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo;X is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, -or -N(Ry)C(0)-;Ring B is selected from the group consisting of:#\#Iand RB, each of which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X;W is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, or -N(Ry)C(0)-;Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more Rc;Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, -OC(O), Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, C(0)0-Ci-ioalkylene, Ci-ioalkyleneC(0)0-, C(0)0-Ci-ioalkyleneC(0)0-, Ci- ioalkyleneC(0)0-Ci-ioalkylene, -OC(0)Ci-ioalkylene, Ci-ioalkylene-OC(O), -OC(0)Ci-ioalkylene-OC(0), Ci-ioalkylene-OC(0)Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-© i-walkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)N(Ry)-, C(0)N(Ry)-(6-to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)C(0), -N(Ry)C(0)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6-to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroaryl ene)C(O), C(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)C(O), -N(Ry)C(0)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-©-, -O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4-to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)C(0), -N(Ry)C(0)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)C(O), -N(Ry)C(0)(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene;wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8- membered cycloalkylene of Linker are independently optionally substituted with RLb; andwherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc;Ring D is optional, and when present is 4- to 12-membered heterocyclyl or 3-to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD; andRing 4 is phenyl optionally substituted with one or more R4a, 5- to 10-membered heteroaryl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b;wherein Ring 4 and Ring 1 are connected via a bond, -N(Ry)-, -O-, - C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, -OC(O), or Ci-ioalkyleneoptionally substituted with one or more oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(0)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(0)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with OH or C(O)Ci-4alkyl;each Rlb, R2b, R3b, and R4bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci- 4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with OH or C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl; andeach Rc, RD, RLb, and RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;wherein Q is Ring 3 or of formula (i) when R1is H, R2is H, and Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0077] In one aspect, provided is a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Q is absent or is Ring 3,wherein Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8- membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12- membered heterocyclyl optionally substituted with one or more R3b;or Q is of formula (i):wherein:Ring A is selected from the group consisting of:H n°-^N^.O HN— &, and each of which is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo;X is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, -or -N(Ry)C(0)-;Ring B is selected from the group consisting of:with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X;W is a bond, -O-, -CH2-, -N(Ry)-, -C(O)N(Ry)-, or -N(Ry)C(O)-;Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more Rc;Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-,Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6-to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-memberedheterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12- membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-Ci- walkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci- walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-Ci-ioalkylene,wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8- membered cycloalkylene of Linker are independently optionally substituted with RLb; andwherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc;Ring D is optional, and when present is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD; andRing 4 is phenyl optionally substituted with one or more R4a, 4- to 12- membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8- membered cycloalkyl optionally substituted with one or more R4b;each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with C(O)Ci-4alkyl;each Rlb, R2b, R3b, and R4bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl; andeach Rc, RD, RLb, and RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;wherein Q is Ring 3 or of formula (i) when R1is H, R2is H, and Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0078] In some embodiments, R1and R2are each F. In some embodiments, R1and R2are each H. In some embodiments, R1is H and R2is F. In some embodiments, R1and R2are taken together to form oxo. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form 3- to 5-membered cycloalkyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form cyclopentyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form cyclobutyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form cyclopropyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form 3- to 5-membered heterocyclyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form oxetanyl, azetidinyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, or tetrahydrothiophenyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form oxetanyl. In some embodiments, R1and R2are taken together along with the atoms to which they are attached to form azetidinyl.

[0079] In some embodiments, m is 0. In some embodiments, m is 1.

[0080] In some embodiments, R3, R4, and R5are each H. In some embodiments, R3, R4, and R5are each independently Ci-4alkyl. In some embodiments, R3, R4, and R5are each independently Ci-2alkyl. In some embodiments, R3, R4, and R5are each ethyl. In some embodiments, R3, R4, and R5are each methyl. In some embodiments, R5is H, and R4and R5are each independently Ci-2alkyl. In some embodiments, R5is H, and R4and R5are each ethyl. In some embodiments, R5is H, and R4and R5are each methyl. In some embodiments, R5is Ci-2alkyl, and R4and R5are each H. In some embodiments, R5is ethyl, and R4and R5are each H. In some embodiments, R5is methyl, and R4and R5are each H. In some embodiments, R3and R4are each Ci-4alkyl. In some embodiments, R3and R4are each methyl or ethyl. In some embodiments, R3and R4are each ethyl. In some embodiments, R5is H.

[0081] In some embodiments, Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3-to 8-membered cycloalkyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 5- to 6-membered heteroaryl optionally substituted with one or more Rla, phenyl optionally substituted with one or more Rla, 4- to 8-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 6-membered cycloalkyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 5- or 6-membered heteroaryl optionally substituted with one or more Rla, phenyl optionally substituted with one or more Rla, 5- to 6-membered heterocyclyl optionally substituted with one or more Rlb, or 4-to 6-membered cycloalkyl optionally substituted with one or more Rlb.

[0082] In some embodiments, Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rlaor 6- to 10-membered aryl optionally substituted with one or more Rla.

[0083] In some embodiments, Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 5- to 6-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 6- to 10-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 5-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 6-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 9-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 10-membered heteroaryl optionally substitutedwith one or more Rla. In some embodiments, Ring 1 is pyrrolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, pyrazolyl, furanyl, thiophenyl, pyridinyl, pyrimidinyl, pyrazinyl, benzothiophenyl, benzimidazolyl, or benzoxazolyl.

[0084] In some embodiments, Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 5- to 6-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 6- to 10-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 5-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 6-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 9-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is 10-membered heteroaryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is pyrrolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, pyrazolyl, furanyl, thiophenyl, pyridinyl, pyrimidinyl, pyrazinyl, benzothiophenyl, benzimidazolyl, or benzoxazolyl, each of which is optionally substituted with one or more Rla.

[0085] In some embodiments, Ring 1 is 6- to 10-membered aryl optionally substituted with one or more Rla. In some embodiments, Ring 1 is phenyl optionally substituted with one or more Rla. In some embodiments, Ring 1 is naphthyl optionally substituted with one or more Rla.In some embodiments, Ring 1 is, each of which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I). In some embodiments, Ring 1 is, each of which is optionallysubstituted with one or more Rla, wherein indicates the point of attachment to -C(O)NR5- of Formula (I). In some embodiments, Ring 1 iswhich is optionally substituted with one or more Rla, whereinindicates the point of attachment to-C(0)NR5- of Formula (I). In some embodiments, Ring 1 isN, which is optionally substituted with one or more Rla, wherein Xv, indicates the point of attachment to-C(0)NR5- of Formula (I). In some embodiments, Ring 1 isN'NH, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I). In some embodiments, Ring 1 iswhich is optionally substituted with one or more Rla, whereinindic aates the point of attachment toN- ui I uiniuia in sonic ciiiuuuiiiicins, ixing i isNwhich is optionally substituted with one or more Rla, whereinindicates the point of attachment to-C(0)NR - of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -ot ormula (I). In some embodiments, Ring 1 is H which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to - QC(0)NR - of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to - QC(0)NR5- of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, wherein indicates the point of attachment toQ-C(0)NR5- of Formula (I). In some embodiments, Ring 1 isHN"- / , which is optionally substituted with one or more Rla, whereinindicates the point of attachment to - QC(O)NR5- of Formula (I). In some embodiments, Ring 1 isN , which is optionally substituted with one or more Rla, whereinindicates the point of attachment to - QC(O)NR5- of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to - QC(O)NR5- of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to - Q-n- C(0)NR5- of Formula (I). In some embodiments, Ring 1 is, which is optionally substituted with one or more Rla, whereinindicates the point of attachment to-C(0)NR5- of Formula (I). In some embodiments, Ring 1is Q' H N Q Q Q-NXQ-<\ N'N T r Q' H % Q N, each of which is optionally substituted with one or more Rla, wherein' indicates the point of attachment to -C(0)NR5- of Formula (I). In some embodiments, Ring 1N^\ 8IorQ , each of which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I). In some embodiments, Ring 1 is:each of which is optionally substituted with one or more Rla. In some embodiments, Ring 1 is, each of which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I).Q

[0086] In some embodiments, Ring 1is , which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(O)NR5- ofFormula (I). In some embodiments, Ring 1 isQ , which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- ofHFormula (I). In some embodiments, Ring 1is Q , which is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I).In some embodiments, Ring 1 isNwhich is optionally substituted with one or more Rla, whereinindicates the point of attachment to -C(0)NR5- of Formula (I). In Q-<\ Tsome embodiments, Ring 1 is N'NH, which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someTXTembodiments, Ring 1 is N , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1is Q , which is optionally substituted with one or more Rla, wherein **, indicates the point of attachment to -C(0)NR5- of Formula (I). In someCL .N. Vembodiments, Ring 1 is, which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 isCT ^^N , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 is, which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 is, which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someXembodiments, Ring 1 isN, which is optionally substituted with one or more R , wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 isHN'N , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 is XX / H ^ which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 is X H , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 isHN-< / ’ , which is optionally substituted with one or more Rla,wherein *"*- indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 isQ , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1is Q'N, which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 isQ , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1 isQ , which is optionally substituted with one or more R , wherein indicates the point of attachment to -C(0)NR5- of Formula (I). In someembodiments, Ring 1is QN, which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(O)NR5- of Formula (I). In some N<\ >i / )~l- ^<7 ’embodiments, Ring 1 isQ , which is optionally substituted with one or more Rla, wherein indicates the point of attachment to -C(O)NR5- of Formula (I). In someembodiments, Ring 1 isN , which is optionally substituted with one or more R , wherein indicates the point of attachment to -C(0)NR5- of Formula (I).

[0087] In some embodiments, Ring 1 is substituted with one or more Rlaor Rlb. In some embodiments, Ring 1 is unsubstituted.CNwherein indicates the point of attachment to -C(O)NR5-indicates the point of attachment to -C(0)NR5- of Formula (I).

[0089] In some embodiments, Ring 1 is 4- to 12-membered heterocyclyl optionally substituted with one or more Rlbor 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 4- to 8-membered heterocyclyl optionally substituted with one or more Rlbor 3- to 6-membered cycloalkyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 5- to 6-membered heterocyclyl optionally substituted with one or more Rlbor 4- to 6-membered cycloalkyl optionally substituted with one or more Rlb.

[0090] In some embodiments, Ring 1 is 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 4- to 8-membered heterocyclyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 4-to 6-membered heterocyclyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is oxetanyl, azetidinyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, or tetrahydropyranyl, each of which is optionally substituted with one or more Rlb.

[0091] In some embodiments, Ring 1 is 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is 4- to 6-membered cycloalkyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is cyclobutyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is cyclopentyl optionally substituted with one or more Rlb. In some embodiments, Ring 1 is cyclohexyl optionally substituted with one or more Rlb.

[0092] In some embodiments, Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b. In some embodiments, Ring 2 is phenyl optionally substituted with one or more R2a, 6-membered heteroaryl optionally substituted with one or more R2a, or 5- to 6-membered heterocyclyl optionally substituted with one or more R2b.

[0093] In some embodiments, Ring 2 is substituted with one or more R2aor R2b. In some embodiments, Ring 2 is unsubstituted.

[0094] In some embodiments, Ring 2 is phenyl optionally substituted with one or more R2a.In some embodiments, Ring 2 isIn some embodiments, Ring 2 issome embodiments, Ring 2 isRing 2is

[0095] In some embodiments, Ring 2 is 5- to 6-membered heteroaryl optionally substituted with one or more R2aor 4- to 12-membered heterocyclyl optionally substituted with one ormore R2b. In some embodiments, Ring 2 is 5- to 6-membered heteroaryl optionally substituted with one or more R2a. In some embodiments, Ring 2 is 6-membered heteroaryl optionally substituted with one or more R2a. In some embodiments, Ring 2 is pyridyl optionally substituted with one or more R2a. In some embodiments, Ring 2 is 4- to 12-membered heterocyclyl optionally substituted with one or more R2b. In some embodiments, Ring 2 is 5- to 6-membered heterocyclyl optionally substituted with one or more R2b. In some embodiments, Ring 2 is pyridone, which is optionally further substituted with R2b. In some O oembodiments, Ring 2is , or

[0096] In some embodiments, Q is absent and the compound is of Formula (II):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1, Ring 2, R1, R2, R3, R4, R5, and m are as described for Formula (I), and wherein R2is F, R1and R2are taken together to form oxo, or R1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl when Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0097] In some embodiments, Q is absent and the compound is of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;each Rlaand R2ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Cl.4alkylene-N(Rv)C(O)Cl.4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlaand R2ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlaand R2ais optionally substituted with oxo, OH, or C(0)Ci-4alkyl;each Rlband R2bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(0)Ci-4alkyl of Rlband R2bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlband R2bis optionally substituted with oxo, OH, or C(0)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;wherein R2is F, R1and R2are taken together to form oxo, or R1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3-to 5-membered heterocyclyl when Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3-to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0098] In some embodiments, Q is absent and the compound is of Formula (II),or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;each Rlaand R2ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlaand R2ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlaand R2ais optionally substituted with C(O)Ci-4alkyl;each Rlband R2bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci- 4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlband R2bis optionally substituted with N(Ry)(Rz), andwherein the 4- to 12-membered heterocyclyl of Rlband R2bis optionally substituted with C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl; andn is 1 or 2;wherein R2is F, R1and R2are taken together to form oxo, or R1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3-to 5-membered heterocyclyl when Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3-to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0099] In some embodiments, Q is Ring 3 and the compound is of Formula (III):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1, Ring 2, Ring 3, R1, R2, R3, R4, R5, and m are as described for Formula (I).

[0100] In some embodiments, Q is Ring 3 and the compound is of Formula (III), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8-membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12-membered heterocyclyl optionally substituted with one or more R3b;each Rla, R2a, and R3a, is independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(0)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rla, R2a, and R3ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, and R3ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rlb, R2b, and R3b, and is independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci- 4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, and R3bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, and R3bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2.

[0101] In some embodiments, Q is Ring 3 and the compound is of Formula (III), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyloptionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8-membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12-membered heterocyclyl optionally substituted with one or more R3b;each Rla, R2a, and R3aindependently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rla, R2a, and R3ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, and R3ais optionally substituted with C(O)Ci-4alkyl;each Rlb, R2b, and R3bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, and R3bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, and R3bis optionally substituted with C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl; andn is 1 or 2.

[0102] In some embodiments, Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8-membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12-membered heterocyclyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is 5- to 6-membered heteroaryl optionally substituted with one or more R3a, phenyl optionally substituted with one or more R3a, 3- to 6-membered cycloalkyl optionally substituted with one or more R3b, or 4- to 8-membered heterocyclyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is 5- to 6-membered heteroaryl optionally substituted with one or more R3a, phenyl optionally substituted with one or more R3a, 4- to 6-membered cycloalkyl optionally substituted with one or more R3b, or 5-to 6-membered heterocyclyl optionally substituted with one or more R3b.

[0103] In some embodiments, Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3aor 6- to 10-membered aryl optionally substituted with one or more R3a.

[0104] In some embodiments, Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a. In some embodiments, Ring 3 is 5- to 6-membered heteroaryl optionally substituted with one or more R3a. In some embodiments, Ring 3 is 5-membered heteroaryl optionally substituted with one or more R3a. In some embodiments, Ring 3 is 6-membered heteroaryl optionally substituted with one or more R3a. In some embodiments, Ring 3 is pyrrolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, pyrazolyl, furanyl, thiophenyl, pyridinyl, pyrimidinyl, pyrazinyl, benzothiophenyl, benzimidazolyl, or benzoxazolyl.

[0105] In some embodiments, Ring 3 is 6- to 10-membered aryl optionally substituted with one or more R3a. In some embodiments, Ring 3 is phenyl optionally substituted with one or more R3a. In some embodiments, Ring 3 is naphthyl optionally substituted with one or more R3a.

[0106] In some embodiments, Ring 3 is 3- to 8-membered cycloalkyl optionally substituted with one or more R3bor 4- to 12-membered heterocyclyl optionally substituted with one or more R3b.

[0107] In some embodiments, Ring 3 is 3- to 8-membered cycloalkyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is 4- to 6-membered cycloalkyloptionally substituted with one or more R3b. In some embodiments, Ring 3 is cyclobutyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is cyclopentyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is cyclohexyl optionally substituted with one or more R3b.

[0108] In some embodiments, Ring 3 is 4- to 12-membered heterocyclyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is 4- to 8-membered heterocyclyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is 4-to 6-membered heterocyclyl optionally substituted with one or more R3b. In some embodiments, Ring 3 is oxetanyl, azetidinyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, or tetrahydropyranyl, each of which is optionally substituted with one or more R3b.

[0109] In some embodiments, Ring 3 is substituted with one or more R3aor R3b. In some embodiments, Ring 3 is unsubstituted.

[0110] In some embodiments, Ring 3is each of which isoptionally substituted with one or more R3b, orwhich is optionally substituted withone or more R3a. In some embodiments, Ring 3 iswhich is optionally substitutedwith one or more R3b. In some embodiments, Ring 3 is, which is optionallyHsubstituted with one or more R3b. In some embodiments, Ring 3is which isoptionally further substituted with one or more R3b. In some embodiments, Ring 3 is, which is optionally substituted with one or more R3a.

[0111] In some embodiments, Ring 3 iseach of which is optionally substituted with one or more R3b.

[0112] In some embodiments, Ring 3 is

[0113] In some embodiments, Q is of Formula (i) and the compound is of Formula (IV):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring A, X, Ring B, W, Ring C, Linker, Ring D, Ring 4, Ring 1, Ring 2, R1, R2, R3, R4, R5, and m are as described for Formula (I).

[0114] In some embodiments, Q is of Formula (i) and the compound is of Formula (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Ring A is selected from the group consisting of:optionally substituted with one or more groups independently selected from Ci-4alkyl and halo;X is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, -or -N(Ry)C(0)-;Ring B is selected from the group consisting of:o, each of which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X;W is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, or -N(Ry)C(0)-;Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl optionally substituted with one or more Rc, 3- to 8-membered cycloalkyl optionally substituted with one or more Rc, 6- to 10-membered aryl optionally substituted with one or more RCa, or 5- to 10-membered heteroaryl optionally substituted with one or more RCa;Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, - OC(O), Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci- ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene- C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci- ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, C(0)0-Ci-ioalkylene, Ci-ioalkyleneC(O)©-, C(0)0-Ci-ioalkyleneC(0)0-, Ci- ioalkyleneC(0)0-Ci-ioalkylene, -OC(0)Ci-ioalkylene, Ci-ioalkylene-OC(O), -OC(0)Ci-ioalkylene-OC(0), Ci-ioalkylene-OC(0)Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-© i-walkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, -(6- to 10-membered arylene)-O-, -O-(6-to 10-membered arylene)-, -(6- to 10-membered arylene)-O-(6- to 10-membered arylene)-, -O-(6- to 10-membered arylene)-O-, -(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-O-(5- to 10-membered heteroarylene)-, -O-(5- to 10-membered heteroarylene)-O-, -(4-to 12-membered heterocyclylene)-©-, -O-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-O-(4- to 12-membered heterocyclylene)-, -O-(4- to 12-membered heterocyclylene)-©-, -(3- to 8-membered cycloalkylene)-©-, -O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-O-(3- to 8-membered cycloalkylene)-, -O-(3- to 8-membered cycloalkylene)-©-, -(6- to 10-membered arylene)-C(O)-, -C(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)-(6- to 10-membered arylene)-, -C(O)-(6- to 10-membered arylene)-C(O)-, -(5- to 10-membered heteroarylene)-C(O)-, -C(O)-(5- to 10-memberedheteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)-(5- to 10-membered heteroarylene)-, -C(O)-(5- to 10-membered heteroarylene)-C(O)-, -(4- to 12-membered heterocyclylene)-C(O)-, -C(O)-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-C(O)-(4- to 12-membered heterocyclylene)-, -C(O)-(4- to 12-membered heterocyclylene)-C(O)-, -(3- to 8-membered cycloalkylene)-C(O)-, -C(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)-(3- to 8-membered cycloalkylene)-, -C(O)-(3- to 8-membered cycloalkylene)-C(O)-, -(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)-(6- to 10-membered arylene)-, -N(Ry)-(6- to 10-membered arylene)-N(Ry)-, -(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)-(5- to 10-membered heteroarylene)-, -N(Ry)-(5- to 10-membered heteroarylene)-N(Ry)-, -(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)-(4- to 12-membered heterocyclylene)-, -N(Ry)-(4- to 12-membered heterocyclylene)-N(Ry)-, -(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)-(3- to 8-membered cycloalkylene)-, -N(Ry)-(3- to 8-membered cycloalkylene)-N(Ry)-, -(6- to 10-membered arylene)-C(O)N(Ry)-, -C(0)N(Ry)-(6- to 10-membered arylene)-, -(6-to 10-membered arylene)-C(0)N(Ry)-(6- to 10-membered arylene)-, -C(0)N(Ry)-(6-to 10-membered arylene)-C(O)N(Ry)-, -(5- to 10-membered heteroarylene)-C(0)N(Ry)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-(5- to 10-membered heteroarylene)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -(4- to 12-membered heterocyclylene)-C(0)N(Ry)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)N(Ry)-(4- to 12-membered heterocyclylene)-, -C(0)N(Ry)-(4-to 12-membered heterocyclylene)-C(O)N(Ry)-, -(3- to 8-membered cycloalkylene)-C(0)N(Ry)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-(3- to 8-membered cycloalkylene)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -(6- to 10-membered arylene)-N(Ry)C(O)-, -N(Ry)C(0)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)C(O)-(6- to 10-membered arylene)-, -N(Ry)C(0)-(6- to 10-membered arylene)-N(Ry)C(O)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -N(Ry)C(0)-(5- to 10-memberedheteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-(5- to 10-membered heteroarylene)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-(4- to 12-membered heterocyclylene)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-N(Ry)C(0)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-(3- to 8-membered cycloalkylene)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-N(Ry)C(0)-, -(6- to 10-membered arylene)-C(O)O-, -C(O)O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)O-(6- to 10-membered arylene)-, -C(O)O-(6- to 10-membered arylene)-C(O)O-, -(5- to 10-membered heteroarylene)-C(O)O-, -C(O)O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)O-(5- to 10-membered heteroarylene)-, -C(O)O-(5- to 10-membered heteroarylene)-C(O)O-, -(4- to 12-membered heterocyclylene)-C(O)O-, -C(O)O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)O-(4- to 12-membered heterocyclylene)-, -C(O)O-(4- to 12-membered heterocyclylene)-C(O)O-, -(3- to 8-membered cycloalkylene)-C(O)O-, -C(O)O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)O-(3- to 8-membered cycloalkylene)-, -C(O)O-(3- to 8-membered cycloalkylene)-C(O)O-, -(6-to 10-membered arylene)-OC(O)-, -OC(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-OC(O)-(6- to 10-membered arylene)-, -OC(O)-(6- to 10-membered arylene)-OC(O)-, -(5- to 10-membered heteroarylene)-OC(O)-, -OC(O)-(5-to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-OC(O)-(5- to 10-membered heteroarylene)-, -OC(O)-(5- to 10-membered heteroarylene)-OC(O)-, -(4- to 12-membered heterocyclylene)-OC(O)-, -OC(O)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-OC(O)-(4- to 12-membered heterocyclylene)-, -OC(O)-(4- to 12-membered heterocyclylene)-OC(O)-, -(3- to 8-membered cycloalkylene)-OC(O)-, -OC(O)-(3- to 8-membered cycloalkylene)-, -(3-to 8-membered cycloalkylene)-OC(O)-(3- to 8-membered cycloalkylene)-, -OC(O)-(3- to 8-membered cycloalkylene)-OC(O)-, Ci-ioalkylene-(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)N(Ry)-, C(O)N(Ry)-(6-to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)C(0), -N(Ry)C(0)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6-to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroaryl ene)C(O), C(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)C(O), -N(Ry)C(0)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-O-, -O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4-to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)C(0), -N(Ry)C(0)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)C(O), -N(Ry)C(0)(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8- membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene;wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8- membered cycloalkylene of Linker are independently optionally substituted with RLb; andwherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc;Ring D is optional, and when present is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD; andRing 4 is phenyl optionally substituted with one or more R4a, 5- to 10- membered heteroaryl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b;wherein Ring 4 and Ring 1 are connected via a bond, -N(Ry)-, -O-, - C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, -OC(O), or Ci-ioalkylene optionally substituted with one or more oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each Rla, R2a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Cl.4alkylene-N(Rv)C(O)Cl.4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rla, R2a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, and R4ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rlb, R2b, and R4bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, and R4bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl; andeach Rc, RD, RLb, and RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each RCais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;wherein Q is Ring 3 or of formula (i) when R1is H, R2is H, and Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0115] In some embodiments, Q is of Formula (i) and the compound is of Formula (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Ring A is selected from the group consisting of:each of which is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo;X is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, -or -N(Ry)C(0)-;Ring B is selected from the group consisting of:or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X;W is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, or -N(Ry)C(0)-;Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more Rc;Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, Ci-ioalkylene, C(O)Ci- walkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-walkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-Ci-ioalkylene,wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8-membered cycloalkylene of Linker are independently optionally substituted with RLb; and wherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc; Ring D is optional, and when present is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD; andRing 4 is phenyl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b;each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with C(O)Ci-4alkyl;each Rlb, R2b, R3b, and R4bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci- 4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl; andeach Rc, RD, RLb, and RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci- 4haloalkyl.

[0116] In some embodiments, Ring A is selected from the group consisting ofeach of which is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo. In some embodiments, RingA is, which is optionally substituted with one or more groups independentlyselected from Ci-4alkyl and halo. In some embodiments, Ring A iswhich is optionally substituted with one or more groups independently selected from Ci-4alkyl and Hhalo. In some embodiments, Ring A iswhich is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo. In some embodiments, RingA is, which is optionally substituted with one or more groups independently selected from Ci-4alkyl and halo.

[0117] In some embodiments, Ring A is substituted with one or more groups independently selected from Ci-4alkyl and halo. In some embodiments, Ring A is unsubstituted.

[0118] In some embodiments, Ring A is

[0119] In some embodiments, X is a bond, -O-, -CH2-, -N(Ry)-, -C(O)N(Ry)-, -or -N(Ry)C(O)-. In some embodiments, X is a bond or -N(Ry)-. In some embodiments, X is a bond. In some embodiments, X is -O-. In some embodiments, X is -CH2-. In some embodiments, X is -N(Ry)-. In some embodiments, X is -C(O)N(Ry)-. In some embodiments, X is -N(Ry)C(O)-.

[0120] In some embodiments, Ring B is selected from the group consisting ofone or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X. In some embodiments,each of which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and, wherein # indicates attachment to X.In some embodiments, Ring B ismore groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X. In some embodiments, Ring B isOo , which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein# indicates attachment to X. In some embodiments, Ring Bis which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X.#In some embodiments, Ring Bis RB, which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X. In some embodiments, Ring B is #\°=< J0JTH", which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein #t# indicates attachment to X. In some embodiments, Ring Bis RB, which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X.In some embodiments, Ring B is, which is optionally substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X. In some embodiments, Ring B is#IRB, which is optionally substituted with one or more groups independentlyselected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X.

[0121] In some embodiments, RBis H. In some embodiments, RBis Ci-4alkyl. In some embodiments, RBis methyl.

[0122] In some embodiments, Ring B is substituted with one or more groups independently selected from halo, Ci-4alkyl, Ci-4haloalkyl, or OH. In some embodiments, Ring B is unsubstituted.#

[0123] In some embodiments, Ring Bis I wherein # indicates attachment to X.

[0124] In some embodiments, W is a bond, -O-, -CH2-, -N(Ry)-, -C(O)N(Ry)-, or -N(Ry)C(O)-. In some embodiments, W is a bond or -CH2-. In some embodiments, W is a bond. In some embodiments, W is -O-. In some embodiments, W is -CH2-. In some embodiments, W is -N(Ry)-. In some embodiments, W is -C(O)N(Ry)-. In some embodiments, W is -N(Ry)C(O)-.

[0125] In some embodiments, Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl optionally substituted with one or more Rc, 3- to 8-membered cycloalkyl optionally substituted with one or more Rc, 6- to 10-membered aryl optionally substituted with one or more RCa, or 5- to 10-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is absent and W is a bond. In some embodiments, Ring C is 4- to 12-membered heterocyclyl optionally substituted with one or more Rc, 3- to 8-membered cycloalkyl optionally substituted with one or more Rc, 6- to 10-membered aryl optionally substituted with one or more RCa, or 5- to 10-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is 4- to 8-membered heterocyclyl optionally substituted with one or more Rc, 3- to 6-membered cycloalkyl optionally substituted with one or more Rc, phenyl optionally substituted with one or more RCa, or 5- to 6-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more Rc. In some embodiments, Ring C is 4- to 8-membered heterocyclyl or 3- to 6-membered cycloalkyl, each of which is optionally substituted with one or more Rc. In some embodiments, Ring C is 5- to 6-membered heterocyclyl or 4- to 6-membered cycloalkyl, each of which is optionally substituted with one or more Rc. In some embodiments, Ring C is 6- to 10-membered aryl optionally substituted with one or more RCa, or 5- to 10-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is phenyl optionally substituted with one or more RCa, or 5- to 6-membered heteroaryl optionally substituted with one or more RCa.

[0126] In some embodiments, Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more Rc. In some embodiments, Ring C is absent and W is a bond. In some embodiments, Ring C is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more Rc. In some embodiments, Ring C is 4- to 8-membered heterocyclyl or 3- to 6-membered cycloalkyl, each of which is optionally substituted with one or more Rc. In some embodiments, Ring C is 5- to 6-membered heterocyclyl or 4- to 6-membered cycloalkyl, each of which is optionally substituted with one or more Rc.

[0127] In some embodiments, Ring C is 4- to 12-membered heterocyclyl optionally substituted with one or more Rc. In some embodiments, Ring C is 4- to 8-membered heterocyclyl optionally substituted with one or more Rc. In some embodiments, Ring C is 4-to 6-membered heterocyclyl optionally substituted with one or more Rc. In some embodiments, Ring C is oxetanyl, azetidinyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, or tetrahydropyranyl, each of which is optionally substituted with one or more Rc.

[0128] In some embodiments, Ring C is 3- to 8-membered cycloalkyl optionally substituted with one or more Rc. In some embodiments, Ring C is 4- to 6-membered cycloalkyl optionally substituted with one or more Rc. In some embodiments, Ring C is cyclobutyl optionally substituted with one or more Rc. In some embodiments, Ring C is cyclopentyl optionally substituted with one or more Rc. In some embodiments, Ring C is cyclohexyl optionally substituted with one or more Rc.

[0129] In some embodiments, Ring C is 6- to 10-membered aryl optionally substituted with one or more RCa. In some embodiments, Ring C is phenyl optionally substituted with one or more RCa. In some embodiments, Ring C is naphthyl optionally substituted with one or more RCa.

[0130] In some embodiments, Ring C is 5- to 10-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is 5- to 6-memberedheteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is 5-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is 6-membered heteroaryl optionally substituted with one or more RCa. In some embodiments, Ring C is pyrrolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, pyrazolyl, furanyl, thiophenyl, pyridinyl, pyrimidinyl, pyrazinyl, benzothiophenyl, benzimidazolyl, or benzoxazolyl, each of which is optionally substituted with one or more RCa.

[0131] In some embodiments, Ring C isoptionally substituted with one or more Rc,or , or each of which is optionally substituted with one or more RCa.

[0132] In some embodiments, Ring C isor s5', each of which is optionally substituted with one or more Rc. In some embodiments, Ring C isor each of which is optionally substituted with one or more Rc. Insome embodiments, Ring C iskwhich is optionally substituted with one or more Rc.N IIn some embodiments, Ring C iswhich is optionally substituted with one ormore Rc. In some embodiments, Ring C iswhich is optionally substituted withone or more Rc. In some embodiments, RingC is which is optionally substitutedwith one or more Rc. In some embodiments, Ring C iswhich is optionallysubstituted with one or more Rc. In some embodiments, Ring C iswhich isoptionally substituted with one or more Rc. In some embodiments, Ring C is, which is optionally substituted with one or more Rc.

[0133] In some embodiments, Ring C is un substituted. In some embodiments, Ring C is substituted with one or more Rcor RCa.

[0134] In some embodiments, Ring C is un substituted. In some embodiments, Ring C is substituted with one or more Rc.I L I 1?

[0135] In some embodiments, Ring C isor

[0136] In some embodiments, Ring C is absent and W is a bond.

[0137] In some embodiments, Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(O)N(Ry)-, -N(Ry)C(O)-, C(O)O-, -OC(O), Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(O)Ci- loalkyleneC(O), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-walkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(O)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci.ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, C(0)0-Ci-ioalkylene, Ci-ioalkyleneC(0)0-, C(O)O-Ci-ioalkyleneC(0)0-, Ci-ioalkyleneC(0)0-Ci-ioalkylene, -OC(0)Ci-ioalkylene, Ci-ioalkylene-OC(O), -OC(0)Ci-ioalkylene-OC(0), Ci-ioalkylene-OC(0)Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5-to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-memberedheterocyclylene)-Ci-ioalkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-Ci-ioalkylene, -(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-O-(6- to 10-membered arylene)-, -O-(6-to 10-membered arylene)-O-, -(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-O-(5- to 10-membered heteroarylene)-, -O-(5- to 10-membered heteroarylene)-O-, -(4- to 12-membered heterocyclylene)-O-, -O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-O-(4- to 12-membered heterocyclylene)-, -O-(4- to 12-membered heterocyclylene)-O-, -(3- to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-O-(3- to 8-membered cycloalkylene)-, -O-(3- to 8-membered cycloalkylene)-O-, -(6- to 10-membered arylene)-C(O)-, -C(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)-(6- to 10-membered arylene)-, -C(O)-(6- to 10-membered arylene)-C(O)-, -(5- to 10-membered heteroarylene)-C(O)-, -C(O)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)-(5- to 10-membered heteroarylene)-, -C(O)-(5- to 10-membered heteroarylene)-C(O)-, -(4- to 12-membered heterocyclylene)-C(O)-, -C(O)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)-(4- to 12-membered heterocyclylene)-, -C(O)-(4- to 12-membered heterocyclylene)-C(O)-, -(3- to 8-membered cycloalkylene)-C(O)-, -C(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)-(3- to 8-membered cycloalkylene)-, -C(O)-(3- to 8-membered cycloalkylene)-C(O)-, -(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)-(6- to 10-membered arylene)-, -N(Ry)-(6- to 10-membered arylene)-N(Ry)-, -(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)-(5- to 10-membered heteroarylene)-, -N(Ry)-(5- to 10-membered heteroarylene)-N(Ry)-, -(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4-to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)-(4- to 12-membered heterocyclylene)-, -N(Ry)-(4- to 12-membered heterocyclylene)-N(Ry)-, -(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)-(3- to 8-membered cycloalkylene)-, -N(Ry)-(3- to 8-membered cycloalkylene)-N(Ry)-, -(6- to 10-membered arylene)-C(O)N(Ry)-, -C(0)N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(0)N(Ry)-(6- to 10-memberedarylene)-, -C(0)N(Ry)-(6- to 10-membered arylene)-C(O)N(Ry)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-(5- to 10-membered heteroarylene)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -(4- to 12-membered heterocyclylene)-C(O)N(Ry)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-C(O)N(Ry)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-(3- to 8-membered cycloalkylene)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -(6-to 10-membered arylene)-N(Ry)C(O)-, -N(Ry)C(0)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)C(0)-(6- to 10-membered arylene)-, -N(Ry)C(0)-(6- to 10-membered arylene)-N(Ry)C(O)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)C(0)-(5- to 10-membered heteroarylene)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-(4-to 12-membered heterocyclylene)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-N(Ry)C(0)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-(3- to 8-membered cycloalkylene)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -(6- to 10-membered arylene)-C(O)O-, -C(O)O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)O-(6- to 10-membered arylene)-, -C(O)O-(6- to 10-membered arylene)-C(O)O-, -(5- to 10-membered heteroarylene)-C(O)O-, -C(O)O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)O-(5- to 10-membered heteroarylene)-, -C(O)O-(5-to 10-membered heteroarylene)-C(O)O-, -(4- to 12-membered heterocyclylene)-C(O)O-, -C(O)O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)O-(4- to 12-membered heterocyclylene)-, -C(O)O-(4- to 12-membered heterocyclylene)-C(O)O-, -(3- to 8-membered cycloalkylene)-C(O)O-, -C(O)O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)O-(3- to 8-membered cycloalkylene)-, -C(O)O-(3- to 8-membered cycloalkylene)-C(O)O-, -(6- to 10-membered arylene)-OC(O)-, -OC(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-OC(O)-(6- to 10-membered arylene)-, -OC(O)-(6- to 10-membered arylene)-OC(O)-, -(5- to 10-membered heteroarylene)-OC(O)-, -OC(O)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-OC(O)-(5-to 10-membered heteroarylene)-, -OC(O)-(5- to 10-membered heteroarylene)-OC(O)-, -(4- to 12-membered heterocyclylene)-OC(O)-, -OC(O)-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-OC(O)-(4- to 12-membered heterocyclylene)-, -OC(O)-(4-to 12-membered heterocyclylene)-OC(O)-, -(3- to 8-membered cycloalkylene)-OC(O)-, -OC(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-OC(O)-(3- to 8-membered cycloalkylene)-, -OC(O)-(3- to 8-membered cycloalkylene)-OC(O)-, Ci-ioalkylene-(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-Ci-walkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)N(Ry)-, C(0)N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)C(0), -N(Ry)C(0)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O), C(O)(5-to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)C(O), -N(Ry)C(0)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-©-, -O-(4-to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)C(O), -N(Ry)C(0)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-memberedheterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)C(0), -N(Ry)C(0)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene;wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8-membered cycloalkylene of Linker are independently optionally substituted with RLb; andwherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc.

[0138] In some embodiments, Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, -OC(O), Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(O)Ci- loalkyleneC(O), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-walkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, C(0)0-Ci-ioalkylene, Ci-ioalkyleneC(0)0-, C(O)O-Ci-ioalkyleneC(0)0-, Ci-ioalkyleneC(0)0-Ci-ioalkylene, -OC(0)Ci-ioalkylene, Ci-ioalkylene-OC(O), -OC(0)Ci-ioalkylene-OC(0), Ci-ioalkylene-OC(0)Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5-to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-memberedheteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-© i-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)N(Ry)-, C(0)N(Ry)-(6- to 10-membered arylene)-Ci-walkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)C(O), -N(Ry)C(0)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O), C(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)C(O), -N(Ry)C(0)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-©-, -O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)C(0), -N(Ry)C(0)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4-to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)-Ci-walkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)C(0), -N(Ry)C(0)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene. In some embodiments, each 6- to 10-membered arylene and 5-to 10-membered heteroarylene of Linker are independently optionally substituted with RLa; each 4- to 12-membered heterocyclylene and 3- to 8-membered cycloalkylene of Linker are independently optionally substituted with RLb; and each Ci-ioalkylene of Linker is independently optionally substituted with RLc.

[0139] In some embodiments, each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently substituted with RLa; each 4- to 12-membered heterocyclylene and 3- to 8-membered cycloalkylene of Linker are independently substituted with RLb; and each Ci-ioalkylene of Linker is independently substituted with RLc.

[0140] In some embodiments, each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are unsubstituted; each 4- to 12-membered heterocyclylene and 3- to 8-membered cycloalkylene of Linker are unsubstituted; and each Ci-ioalkylene of Linker is unsubstituted.

[0141] In some embodiments, Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-walkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-0-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(O)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci- ioalkylene-N(Ry)C(0)-Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-memberedarylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-Ci-ioalkylene.

[0142] In some embodiments, Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-O-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, 6- to 10-membered aryl optionally substituted with RLa, 5- to 10-membered heteroaryl optionally substituted with RLa, 4- to 12-membered heterocyclyl optionally substituted with RLb, or 3- to 8-membered cycloalkyl optionally substituted with RLb. In some embodiments, Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, Ci-7alkylene, C(O)Ci-7alkylene, Ci-7alkyleneC(O), C(O)Ci-7alkyleneC(O), Ci-7alkyleneC(O)Ci-7alkylene, -N(Ry)-Ci-7alkylene, Ci-7alkylene-N(Ry)-, -N(Ry)-Ci-7alkylene-N(Ry)-, Ci-7alkylene-N(Ry)-Ci-7alkylene, -O-Ci-7alkylene, Ci-7alkylene-O-, -O-Ci-7alkylene-O-, Ci-7alkylene-O-Ci-7alkylene,-C(O)N(Ry)-Ci-7alkylene, Ci-7alkylene-C(O)N(Ry)-, -C(O)N(Ry)-Ci-7alkylene-C(O)N(Ry)-, Ci-7alkylene-C(O)N(Ry)-Ci-7alkylene, -N(Ry)C(O)-Ci-7alkylene, Ci-7alkylene-N(Ry)C(O)-, -N(Ry)C(O)-Ci-7alkylene-N(Ry)C(O)-, Ci-7alkylene-N(Ry)C(O)-Ci-7alkylene, 6- to 10-membered aryl optionally substituted with RLa, 5- to 10-membered heteroaryl optionally substituted with RLa, 4- to 12-membered heterocyclyl optionally substituted with RLb, or 3- to 8-membered cycloalkyl optionally substituted with RLb. In some embodiments, Linker is abond, -O-, -C(O)-, -N(Ry)-, -C(O)N(Ry)-, -N(Ry)C(O)-, Ci-4alkylene, C(O)Ci-4alkylene, Ci-4alkyleneC(O), C(O)Ci-4alkyleneC(O), Ci-4alkyleneC(O)Ci-4alkylene, -N(Ry)-Ci-4alkylene, Ci-4alkylene-N(Ry)-, -N(Ry)-Ci-4alkylene-N(Ry)-, Ci-4alkylene-N(Ry)-Ci-4alkylene, -O-Ci-4alkylene, Ci-4alkylene-O-, -O-Ci-4alkylene-O-, Ci-4alkylene-O-Ci-4alkylene, -C(O)N(Ry)-Ci-4alkylene, Ci-4alkylene-C(O)N(Ry)-,-C(O)N(Ry)-Ci-4alkylene-C(O)N(Ry)-, Ci-4alkylene-C(O)N(Ry)-Ci-4alkylene, -N(Ry)C(O)-Ci-4alkylene, Ci-4alkylene-N(Ry)C(O)-, -N(Ry)C(O)-Ci-4alkylene-N(Ry)C(O)-, Ci-4alkylene-N(Ry)C(O)-Ci-4alkylene, 6- to 10-membered aryl optionally substituted with RLa, 5- to 10-membered heteroaryl optionally substituted with RLa, 4- to 12-membered heterocyclyl optionally substituted with RLb, or 3- to 8-membered cycloalkyl optionally substituted with RLb.

[0143] In some embodiments, Linker is C(O)(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-C(O)-, C(O)(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)C(O)N(Ry)-, C(0)N(Ry)-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)- N(Ry)C(0)-, -N(Ry)C(0)(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)C(O), C(O)(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)C(O), C(O)(5- to 10-membered heteroarylene)-C(O)-, C(O)(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5-to 10-membered heteroarylene)C(O), C(O)(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)C(O), C(O)(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -N(Ry)C(0)(5- to 10-membered heteroarylene)C(O), C(O)(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)C(O), C(O)(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-memberedheteroaryl ene)C(O), C(O)(4- to 12-membered heterocyclylene)-O-, -O-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-C(O)-, C(O)(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-N(Ry)C(O)-, -N(Ry)C(0)(4- to 12-membered heterocyclyl ene)C(O), C(O)(4- to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-membered heterocyclylene)C(O),C(O)(3- to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-C(O)-, C(O)(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -N(Ry)C(0)(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)C(O).

[0144] In some embodiments, Linker is -(6- to 10-membered arylene)-O-, -O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-O-(6- to 10-membered arylene)-, -O-(6-to 10-membered arylene)-O-, -(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-O-(5- to 10-membered heteroarylene)-, -O-(5- to 10-membered heteroarylene)-O-, -(4- to 12-membered heterocyclylene)-O-, -O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-O-(4- to 12-membered heterocyclylene)-, -O-(4- to 12-membered heterocyclylene)-O-, -(3- to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-O-(3- to 8-membered cycloalkylene)-, -O-(3- to 8-membered cycloalkylene)-O-, -(6- to 10-membered arylene)-C(O)-, -C(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)-(6- to 10-membered arylene)-, -C(O)-(6- to 10-membered arylene)-C(O)-, -(5- to 10-membered heteroarylene)-C(O)-, -C(O)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)-(5- to 10-membered heteroarylene)-, -C(O)-(5- to 10-membered heteroarylene)-C(O)-, -(4- to 12-membered heterocyclylene)-C(O)-, -C(O)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)-(4- to 12-membered heterocyclylene)-, -C(O)-(4- to 12-membered heterocyclylene)-C(O)-, -(3- to 8-membered cycloalkylene)-C(O)-, -C(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)-(3- to 8-membered cycloalkylene)-, -C(O)-(3- to 8-membered cycloalkylene)-C(O)-, -(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)-(6- to 10-membered arylene)-, -N(Ry)-(6- to 10-membered arylene)-N(Ry)-, -(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)-(5- to 10-membered heteroarylene)-, -N(Ry)-(5- to 10-membered heteroarylene)-N(Ry)-, -(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4-to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)-(4- to 12-membered heterocyclylene)-, -N(Ry)-(4- to 12-membered heterocyclylene)-N(Ry)-, -(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)-(3- to 8-membered cycloalkylene)-, -N(Ry)-(3- to 8-membered cycloalkylene)-N(Ry)-, -(6- to 10-membered arylene)-C(O)N(Ry)-, -C(0)N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(0)N(Ry)-(6- to 10-membered arylene)-, -C(0)N(Ry)-(6- to 10-membered arylene)-C(O)N(Ry)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-(5- to 10-membered heteroarylene)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -(4- to 12-membered heterocyclylene)-C(O)N(Ry)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-C(O)N(Ry)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-(3- to 8-membered cycloalkylene)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -(6-to 10-membered arylene)-N(Ry)C(O)-, -N(Ry)C(0)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)C(0)-(6- to 10-membered arylene)-, -N(Ry)C(0)-(6- to 10-membered arylene)-N(Ry)C(O)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)C(0)-(5- to 10-membered heteroarylene)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-(4-to 12-membered heterocyclylene)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-N(Ry)C(0)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-(3- to 8-membered cycloalkylene)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -(6- to 10-membered arylene)-C(O)O-, -C(O)O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)O-(6- to 10-membered arylene)-, -C(O)O-(6- to 10-membered arylene)-C(O)O-, -(5- to 10-membered heteroarylene)-C(O)O-, -C(O)O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)O-(5- to 10-membered heteroarylene)-, -C(O)O-(5-to 10-membered heteroarylene)-C(O)O-, -(4- to 12-membered heterocyclylene)-C(O)O-, -C(O)O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)O-(4- to 12-membered heterocyclylene)-, -C(O)O-(4- to 12-membered heterocyclylene)-C(O)O-, -(3- to 8-membered cycloalkylene)-C(O)O-, -C(O)O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)O-(3- to 8-membered cycloalkylene)-, -C(O)O-(3- to 8-membered cycloalkylene)-C(O)O-, -(6- to 10-membered arylene)-OC(O)-, -OC(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-OC(O)-(6- to 10-membered arylene)-, -OC(O)-(6- to 10-membered arylene)-OC(O)-, -(5- to 10-membered heteroarylene)-OC(O)-, -OC(O)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-OC(O)-(5-to 10-membered heteroarylene)-, -OC(O)-(5- to 10-membered heteroarylene)-OC(O)-, -(4- to 12-membered heterocyclylene)-OC(O)-, -OC(O)-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-OC(O)-(4- to 12-membered heterocyclylene)-, -OC(O)-(4-to 12-membered heterocyclylene)-OC(O)-, -(3- to 8-membered cycloalkylene)-OC(O)-, -OC(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-OC(O)-(3- to 8-membered cycloalkylene)-, or -OC(O)-(3- to 8-membered cycloalkylene)-OC(O)-. In some embodiments, each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa; and each 4- to 12-membered heterocyclylene and 3- to 8-membered cycloalkylene of Linker are independently optionally substituted with RLb.

[0145] In some embodiments, Linker is Ci-ioalkyleneC(O), C(0)Ci-ioalkylene, C(O)Ci-loalkyleneC(O), -C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -N(Ry)C(0)-Ci-ioalkylene, or Ci-ioalkylene-N(Ry)C(0)-. In some embodiments, Linker is Ci-8alkyleneC(O), C(O)Ci-8alkylene, C(O)Ci-8alkyleneC(O), -C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, -C(O)N(Ry)-Ci-8alkylene, Ci-8alkylene-C(O)N(Ry)-, -N(Ry)C(O)-Ci-8alkylene, or Ci-8alkylene-N(Ry)C(O)-. In some embodiments, Linker is Ci-7alkyleneC(O), C(O)Ci-7alkylene, C(O)Ci-7alkyleneC(O), -C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, -C(0)N(Ry)-Ci-7alkylene, Ci-7alkylene-C(O)N(Ry)-, -N(Ry)C(O)-Ci-7alkylene, or Ci-7alkylene-N(Ry)C(O)-. In some embodiments, Linker is Ci-4alkyleneC(O), C(O)Ci-4alkylene, C(O)Ci-4alkyleneC(O), -C(O)-,-C(0)N(Ry)-, -N(Ry)C(0)-, -C(O)N(Ry)-Ci-4alkylene, Ci-4alkylene-C(O)N(Ry)-, -N(Ry)C(0)-Ci-4alkylene, or Ci-4alkylene-N(Ry)C(O)-.

[0146] In some embodiments, Linker is Ci-ioalkyleneC(O), C(0)Ci-ioalkylene, C(O)Ci-loalkyleneC(O), -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -N(Ry)C(O)-Ci-walkylene, or Ci-ioalkylene-N(Ry)C(0)-. In some embodiments, Linker is Ci-ioalkyleneC(O), C(0)Ci-ioalkylene, or C(0)Ci-ioalkyleneC(0). In some embodiments, Linker is Ci-7alkyleneC(O), C(O)Ci-7alkylene, or C(O)Ci-7alkyleneC(O). In some embodiments, Linker is C2-7alkyleneC(O), C(O)C2-7alkylene, or C(O)C2-7alkyleneC(O). In some embodiments,Linker is C3-?alkyleneC(0), C(0)C3-?alkylene, or C(0)C3-?alkyleneC(0). In some embodiments, Linker is C4-6alkyleneC(O), C(O)C4-6alkylene, or C(O)C4-6alkyleneC(O).

[0147] In some embodiments, Linker is Ci-ioalkyleneC(O), C(0)Ci-ioalkylene, C(O)Ci-loalkyleneC(O), -C(O)-, C(O)O-, -OC(O), -C(O)N(Ry)-, -N(Ry)C(O)-, -C(O)N(Ry)-Ci-walkylene, Ci-ioalkylene-C(0)N(Ry)-, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, C(O)O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-OC(O).

[0148] In some embodiments, Ring D is optional, and when present, is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD. In some embodiments, Ring D is absent. In some embodiments, Ring D is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD. In some embodiments, Ring D is 4- to 8-membered heterocyclyl or 3- to 6-membered cycloalkyl, each of which is optionally substituted with one or more RD. In some embodiments, Ring D is 5- to 6-membered heterocyclyl or 4- to 6-membered cycloalkyl, each of which is optionally substituted with one or more RD.

[0149] In some embodiments, Ring D is 4- to 12-membered heterocyclyl optionally substituted with one or more RD. In some embodiments, Ring D is 4- to 8-membered heterocyclyl optionally substituted with one or more RD. In some embodiments, Ring D is 4-to 6-membered heterocyclyl optionally substituted with one or more RD. In some embodiments, Ring D is oxetanyl, azetidinyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, or tetrahydropyranyl, each of which is optionally substituted with one or more RD.

[0150] In some embodiments, Ring D is 3- to 8-membered cycloalkyl optionally substituted with one or more RD. In some embodiments, Ring D is 4- to 6-membered cycloalkyl optionally substituted with one or more RD. In some embodiments, Ring D is cyclobutyl optionally substituted with one or more RD. In some embodiments, Ring D is cyclopentyl optionally substituted with one or more RD. In some embodiments, Ring D is cyclohexyl optionally substituted with one or more RD.I , L N K NI C _ N-J

[0151] In some embodiments, Ring D isr'', ,oreach of which is optionally substituted with one or more RD. In someL 1?l\x-N'<s>embodiments, Ring D isor each of which is optionally substitutedwith one or more RD. In some embodiments, Ring D is unsubstituted. In some embodiments,Ring D is substituted with one or more RD. In some embodiments, Ring D isIn some embodiments, Ring D isIn some embodiments, Ring D isIn some embodiments, Ring D isIn some embodiments, Ring D is. In some embodiments, Ring D is

[0152] In some embodiments, Ring 4 is phenyl optionally substituted with one or more R4a, 5- to 10-membered heteroaryl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b; wherein Ring 4 and Ring 1 are connected via a bond, -N(Ry)-, -O-, -C(O)-, -C(O)N(Ry)-, -N(Ry)C(O)-, C(O)O-, -OC(O), or Ci-ioalkylene optionally substituted with one or more oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;

[0153] In some embodiments, Ring 4 is phenyl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is phenyl optionally substituted with one or more R4a. In some embodiments, Ring 4 is 5- to 10-membered heteroaryl optionally substituted with one or more R4a. In some embodiments, Ring 4 is 4- to 12-membered heterocyclyl optionally substituted with one or more R4bor 3- to 8-membered cycloalkyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is 4- to 8-membered heterocyclyl optionally substituted with one or more R4bor 3- to 6-membered cycloalkyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is 5- to 6-membered heterocyclyl optionally substituted with one or more R4bor 4- to 6-membered cycloalkyl optionally substituted with one or more R4b.

[0154] In some embodiments, Ring 4 is 5- to 10-membered heteroaryl optionally substituted with one or more R4a. In some embodiments, Ring 4 is 5- to 6-membered heteroaryl optionally substituted with one or more R4a. In some embodiments, Ring 4 is 5-membered heteroaryl optionally substituted with one or more R4a. In some embodiments, Ring 4 is 6-membered heteroaryl optionally substituted with one or more R4a. In someembodiments, Ring 4 is pyridinyl optionally substituted with one or more R4a. In some embodiments, Ring 4 is pyrazolyl optionally substituted with one or more R4a.

[0155] In some embodiments, Ring 4 is 4- to 12-membered heterocyclyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is 4- to 8-membered heterocyclyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is 4-to 6-membered heterocyclyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is oxetanyl, azetidinyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, or tetrahydropyranyl, each of which is optionally substituted with one or more R4b.

[0156] In some embodiments, Ring 4 is 3- to 8-membered cycloalkyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is 4- to 6-membered cycloalkyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is cyclobutyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is cyclopentyl optionally substituted with one or more R4b. In some embodiments, Ring 4 is cyclohexyl optionally substituted with one or more R4b.

[0157] In some embodiments, Ring 4 is phenyl, which is optionally substituted with one or more R4a, or piperazinyl, piperidinyl or cyclohexyl, each of which is optionally substituted with one or more R4b. In some embodiments, Ring 4 is piperidinyl or cyclohexyl, each of which is optionally substituted with one or more R4b. In some embodiments, Ring 4 is piperidinyl, which is optionally substituted with one or more R4b. In some embodiments, Ring 4 is cyclohexyl, which is optionally substituted with one or more R4b. In some embodiments,Ring 4 iseach of which is optionally substituted with one or moreoptionally substituted with one or more R4b. In some embodiments, Ring 4 iswhich is optionally substituted with one or more R4a, or, each of which is optionally substituted with one or more R4b. In someembodiments, Ring 4 iseach of which isoptionally substituted with one or more R4b. In some embodiments, Ring 4 is,, each of which is optionallysubstituted with one or more R4a. In some embodiments, Ring 4 is,r , or i , each of which is optionally substituted with one or more R4a.

[0158] In some embodiments, Ring 4 isIn some embodiments, Ring 4 isIn some embodiments, Ring 4 isIn some embodiments, Ring 4 isIn some embodiments, Ring 4 isIn some embodiments, Ring 4 isIn some embodiments, Ring 4 isIn some embodiments, Ring 4 is

[0159] In some embodiments, Ring 4 and Ring 1 are connected via a bond. In some embodiments, Ring 4 and Ring 1 are connected via -N(Ry)-. In some embodiments, Ring 4 and Ring 1 are connected via -O-. In some embodiments, Ring 4 and Ring 1 are connected via -C(O)-. In some embodiments, Ring 4 and Ring 1 are connected via -C(O)N(Ry)-. Insome embodiments, Ring 4 and Ring 1 are connected via -N(Ry)C(O)-. In some embodiments, Ring 4 and Ring 1 are connected via C(O)O-. In some embodiments, Ring 4 and Ring 1 are connected via -OC(O). In some embodiments, Ring 4 and Ring 1 are connected via Ci-ioalkylene optionally substituted with one or more oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl.

[0160] In some embodiments, each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci- 4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais substituted with OH. In some embodiments, each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci- 4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais substituted with OH.

[0161] In some embodiments, each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci- 4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rla, R2a, R3a, and R4ais independently Ci-4alkyl, C(O)Ci-4alkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionallysubstituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rla, R2a, R3a, and R4ais independently Ci-4alkyl. In some embodiments, each Rla, R2a, R3a, and R4ais independently C(0)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each Rla, R2a, R3a, and R4ais independently C(0)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each Rla, R2a, R3a, and R4ais independently unsubstituted C(0)Ci-4alkyl. In some embodiments, each Rla, R2a, R3a, and R4ais independently C(0)Me. In some embodiments, each Rla, R2a, R3a, and R4ais independently 4- to 12-membered heterocyclyl optionally substituted with OH. In some embodiments, each Rla, R2a, R3a, and R4ais independently 4- to 12-membered heterocyclyl optionally substituted with oxo. In some embodiments, each Rla, R2a, R3a, and R4ais independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Ci-4alkyl. In some embodiments, each Rla, R2a, R3a, and R4ais independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each Rla, R2a, R3a, and R4ais independently 6-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each Rla, R2a, R3a, and R4ais independently piperidinyl optionally substituted with C(0)Me.

[0162] In some embodiments, each Rlais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of Rlais optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each Rlais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of Rlais optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rlais substituted with OH.

[0163] In some embodiments, each Rlais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlais independently Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlais independently Ci-4alkyl. In some embodiments, each Rlais independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each Rlais independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each Rlais independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each Rlais independently C(0)Me. In some embodiments, each Rlais independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlais independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each Rlais independently 6-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each Rlais independently piperidinyl optionally substituted with C(0)Me.

[0164] In some embodiments, each R2ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2ais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R2ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each R2ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2ais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R2ais optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rlais substituted with OH.

[0165] In some embodiments, each R2ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R2ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R2ais independently Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R2ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R2ais independently Ci-4alkyl. In some embodiments, each R2ais independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each R2ais independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each R2ais independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each R2ais independently C(0)Me. In some embodiments, each R2ais independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R2ais independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R2ais independently 6-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R2ais independently piperidinyl optionally substituted with C(0)Me.

[0166] In some embodiments, each R3ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3ais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R3ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each R3ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3ais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R3ais optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of R3ais substituted with OH.

[0167] In some embodiments, each R3ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R3ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R3ais independently Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R3ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R3ais independently Ci-4alkyl. In some embodiments, each R3ais independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each R3ais independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each R3ais independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each R3ais independently C(0)Me. In some embodiments, each R3ais independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R3ais independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R3ais independently 6-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R3ais independently piperidinyl optionally substituted with C(0)Me.

[0168] In some embodiments, each R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4ais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R4ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(0)Ci-4alkyl of R4ais optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R4ais optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rlais substituted with OH.

[0169] In some embodiments, each R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci- 4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R4ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R4ais independently Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R4ais optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R4ais independently Ci-4alkyl. In some embodiments, each R4ais independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each R4ais independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each R4ais independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each R4ais independently C(0)Me. In some embodiments, each R4ais independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R4ais independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R4ais independently 6-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R4ais independently piperidinyl optionally substituted with C(0)Me.

[0170] In some embodiments, each Rlb, R2b, R3b, and R4bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci- 4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with oxo, OH or C(O)Ci-4alkyl. In some embodiments, each Rlb, R2b, R3b, and R4bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis substituted with OH.

[0171] In some embodiments, each Rlb, R2b, R3b, and R4bis independently oxo halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlb, R2b, R3b, and R4bis independently oxo, Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlb, R2b, R3b, and R4bis independently Ci-4alkyl. In some embodiments, each Rlb, R2b, R3b, and R4bis independently oxo. In some embodiments, each Rlb, R2b, R3b, and R4bis independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each Rlb, R2b, R3b, and R4bis independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each Rlb, R2b, R3b, and R4bis independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each Rlb, R2b, R3b, and R4bis independently C(O)Me. In some embodiments, each Rlb, R2b, R3b, and R4bis independently 4- to 12-membered heterocyclyl optionally substituted with OH. In some embodiments, each Rlb, R2b, R3b, and R4bis independently 4- to 12-membered heterocyclyl optionally substituted with oxo. In some embodiments, each Rlb, R2b, R3b, and R4bis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlb, R2b, R3b, and R4bis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each Rlb, R2b, R3b, and R4bis independently 6-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each Rlb, R2b, R3b, and R4bis independently piperidinyl optionally substituted with C(O)Me.

[0172] In some embodiments, each Rlbis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlbis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of Rlbis optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each Rlbis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlbis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of Rlbis optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of Rlbis substituted with OH.

[0173] In some embodiments, each Rlbis independently oxo halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlbis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlbis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlbis independently oxo, Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of Rlbis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlbis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlbis independently Ci-4alkyl. In some embodiments, each Rlbis independently oxo. In some embodiments, each Rlbis independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each Rlbis independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each Rlbis independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each Rlbis independently C(O)Me. In some embodiments, each Rlbis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each Rlbis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each Rlbis independently 6-membered heterocyclyloptionally substituted with C(O)Me. In some embodiments, each Rlbis independently piperidinyl optionally substituted with C(0)Me.

[0174] In some embodiments, each R2bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2bis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R2bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of R2bis substituted with OH. In some embodiments, each R2bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2bis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R2bis optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of R2bis substituted with OH.

[0175] In some embodiments, each R2bis independently oxo halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlbis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R2bis independently oxo, Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R2bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R2bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R2bis independently Ci-4alkyl. In some embodiments, each R2bis independently oxo. In some embodiments, each R2bis independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each R2bis independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each R2bis independently unsubstituted C(O)Ci-4alkyl. In some embodiments, each R2bis independently C(O)Me. In some embodiments, each R2bis independently 4- to12-membered heterocyclyl optionally substituted with C(0)Ci-4alkyl. In some embodiments, each R2bis independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R2bis independently 6-membered heterocyclyl optionally substituted with C(0)Me. In some embodiments, each R2bis independently piperidinyl optionally substituted with C(0)Me.

[0176] In some embodiments, each R3bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3bis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R3bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each R3bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3bis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R3bis optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of R3bis substituted with OH.

[0177] In some embodiments, each R3bis independently oxo halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R3bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R3bis independently oxo, Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R3bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R3bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R3bis independently Ci-4alkyl. In some embodiments, each R3bis independently oxo. In some embodiments, each R3bis independently C(O)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each R3bis independently C(O)Ci-4alkyl substituted with N(Ry)(Rz). In someembodiments, each R3bis independently unsubstituted C(0)Ci-4alkyl. In some embodiments, each R3bis independently C(O)Me. In some embodiments, each R3bis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R3bis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each R3bis independently 6-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each R3bis independently piperidinyl optionally substituted with C(O)Me.

[0178] In some embodiments, each R4bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci-4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4bis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R4bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl. In some embodiments, each R4bis independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkylene-N(Ry)C(O)Ci-4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4bis optionally substituted with N(Ry)(Rz), and wherein the 4-to 12-membered heterocyclyl of R4bis optionally substituted with OH or C(O)Ci-4alkyl. In some embodiments, the 4- to 12-membered heterocyclyl of R4bis substituted with OH.

[0179] In some embodiments, each R4bis independently oxo halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci- 4alkylene-N(Ry)-Ci-4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4-to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R4bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R4bis independently oxo, Ci-4alkyl, C(O)Ci-4alkyl, 4- to 12-membered heterocyclyl; wherein the C(O)Ci-4alkyl of R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of R4bis optionally substituted with C(O)Ci-4alkyl. In some embodiments, each R4bis independently Ci-4alkyl. In some embodiments, each R4bis independently oxo. In some embodiments, eachR4bis independently C(0)Ci-4alkyl optionally substituted with N(Ry)(Rz). In some embodiments, each R4bis independently C(0)Ci-4alkyl substituted with N(Ry)(Rz). In some embodiments, each R4bis independently unsubstituted C(0)Ci-4alkyl. In some embodiments, each R4bis independently C(O)Me. In some embodiments, each R4bis independently 4- to 12-membered heterocyclyl optionally substituted with C(0)Ci-4alkyl. In some embodiments, each R4bis independently 4- to 12-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each R4bis independently 6-membered heterocyclyl optionally substituted with C(O)Me. In some embodiments, each R4bis independently piperidinyl optionally substituted with C(O)Me.

[0180] In some embodiments, each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each Rx, Ry, and Rzis H. In some embodiments, each Rx, Ry, and Rzis independently Ci-4alkyl. In some embodiments, each Rx, Ry, and Rzis independently methyl. In some embodiments, each Rx, Ry, and Rzis independently Ci-4haloalkyl.

[0181] In some embodiments, each Rxis independently H, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each Rxis H. In some embodiments, each Rxis independently Ci-4alkyl. In some embodiments, each Rxis independently methyl. In some embodiments, each Rxis independently Ci-4haloalkyl.

[0182] In some embodiments, each Ryis independently H, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each Ryis H. In some embodiments, each Ryis independently Ci-4alkyl. In some embodiments, each Ryis independently methyl. In some embodiments, each Ryis independently Ci-4haloalkyl.

[0183] In some embodiments, each Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each Rzis H. In some embodiments, each Rzis independently Ci-4alkyl. In some embodiments, each Rzis independently methyl. In some embodiments, each Rzis independently Ci-4haloalkyl.

[0184] In some embodiments, n is 1 or 2. In some embodiments, n is 1. In some embodiments, n is 2.

[0185] In some embodiments, each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each RLais independently halo. In some embodiments, each RLais independently OH. In some embodiments, each RLais Ci-4alkoxy. In some embodiments, each RLais independently Ci-4alkyl. In some embodiments, each RLais independently methyl. In some embodiments, each RLais independently Ci-4haloalkyl.

[0186] In some embodiments, each Rc, RD, RLband RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each Rc, RD, RLband RLcis independently oxo. In some embodiments, each Rc, RD, RLband RLcis independently halo. In some embodiments, each Rc, RD, RLband RLcis independently OH. In some embodiments, each Rc, RD, RLband RLcis Ci-4alkoxy. In some embodiments, each Rc, RD, RLband RLcis independently Ci-4alkyl. In some embodiments, each Rc, RD, RLband RLcis independently methyl. In some embodiments, each Rc, RD, RLband RLcis independently Ci-4haloalkyl.

[0187] In some embodiments, each Rcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each Rcis independently oxo. In some embodiments, each Rcis independently halo. In some embodiments, each Rcis independently OH. In some embodiments, each Rcis Ci-4alkoxy. In some embodiments, each Rcis independently Ci-4alkyl. In some embodiments, each Rcis independently methyl. In some embodiments, each Rcis independently Ci-4haloalkyl.

[0188] In some embodiments, each RDis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each RDis independently oxo. In some embodiments, each RDis independently halo. In some embodiments, each RDis independently OH. In some embodiments, each RDis Ci-4alkoxy. In some embodiments, each RDis independently Ci-4alkyl. In some embodiments, each RDis independently methyl. In some embodiments, each RDis independently Ci-4haloalkyl.

[0189] In some embodiments, each RLbis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each RLbis independently oxo. In some embodiments, each RLbis independently halo. In some embodiments, each RLbis independently OH. In some embodiments, each RLbis Ci-4alkoxy. In some embodiments, each RLbis independently Ci-4alkyl. In some embodiments, each RLbis independently methyl. In some embodiments, each RLbis independently Ci-4haloalkyl.

[0190] In some embodiments, each RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each RLcis independently oxo. In some embodiments, each RLcis independently halo. In some embodiments, each RLcis independently fluoro. In some embodiments, each RLcis independently OH. In some embodiments, each RLcis Ci-4alkoxy. In some embodiments, each RLcis independently Ci-4alkyl. In some embodiments, each RLcis independently methyl. In some embodiments, each RLCis independently Ci-4haloalkyl.

[0191] In some embodiments, each RCais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl. In some embodiments, each RCais independently halo. In some embodiments, each RCais independently OH. In some embodiments, each RCais Ci-4alkoxy. In some embodiments, each RCais independently Ci-4alkyl. In some embodiments, each RCais independently methyl. In some embodiments, each RCais independently Ci-4haloalkyl.

[0192] In some embodiments, Q is Ring 3 or of formula (i) when R1is H, R2is H, and Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0193] In some embodiments, R2is F, R1and R2are taken together to form oxo, or R1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl when Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

[0194] In some embodiments, Ring C and Ring D are each absent and W is a bond. In some embodiments, Ring C and Ring D are each absent, W is a bond, and Linker and Ring 4Bare taken together to formt tn , wherein p is 1-10, and wherein indicates the point of attachment to Ring 1. In some embodiments, Ring C and Ring D are each absent, W is a bond, and Linker and Ring 4 are taken together to form, wherein p is 1-10, and wherein indicates the point of attachmentRing 1. In some embodiments, Ring C and Ring D are each absent, W is a bond, and LinkerBand Ring 4 are taken together to formt tn , wherein p is 1-10, and wherein indicates the point of attachment to Ring 1. In some embodiments, p is 4-10. In some embodiments, p is 4-7. In some embodiments, p is 4. In some embodiments, p is 6.

[0195] In some embodiments, D is absent, and Ring C, Linker, and Ring 4 are taken ML vtogether to form, wherein p is 1-10, and whereinindicates the point of attachment to Ring 1. In some embodiments, p is 4-10. In some embodiments, p is 4-7. In some embodiments, p is 4. In some embodiments, p is 6.

[0196] In some embodiments, the compound of Formula (I) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (Lm), (Ln), (I-o), (Lp), (I-q), (I-r), (I-s), or (I-t):wherein Q, Ring 2, R1, R2, R3, R4, R5, R2a, and m are as defined herein for Formula (I).

[0197] In some embodiments, the compound of Formula (I) is a compound of Formula (IV), wherein the compound of Formula (IV) is a compound of Formula (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-wherein Ring 2, R1, R2, R3, R4, R5, R2a, m, Ring A, X, Ring B, W, Ring C, Linker, Ring D, and Ring 4 are as defined for a compound of Formula (I) or a compound of Formula (IV).

[0198] It is to be understood that all embodiments of Formula (I) and sub-formulas thereof, also apply to Formulas (II), (III), and (IV), including all sub-formulas, and variations thereof, as applicable. Further, the present disclosure contemplates combinations of features as disclosed herein, as if each were individually listed. Exemplary combinations of features are provided herein but are not to be construed as limiting. In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-j), (I-k), (I-m), (I-n), (I-o), (I-p), (I-q), (I-r), (I-s), (I-t), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), (IV-m), (IV-n), (IV-o), (IV-p), (IV-q), (IV-r), (IV-s), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), (IV-aa), (IV-ab), or (IV-ac). In some embodiments, the compound of Formula (I), (II), (III), or (IV) is a compound of Formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), or (IV-j). In some embodiments, the compound is a compound of Formula (I).

[0199] Representative compounds are listed in Table 1 and Table 2.

[0200] In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from Table 1 or Table 2. In some embodiments, provided is a phosphonic acid ethyl ester of a compound of Table 1 or Table 2. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from Table 1. In some embodiments, provided is a phosphonic acid ethyl ester of a compound of Table 1. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of Compounds 1-27 in Table 1. In some embodiments, provided is a phosphonic acid ethyl ester of a compound selected from the group consisting of Compounds 1-27 in Table 1. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of Compounds1-27, 52-56, 126-143, and 169 in Table 1. In some embodiments, provided is a phosphonic acid ethyl ester of a compound selected from the group consisting of Compounds 1-27, 52-56, 126-143, and 169 in Table 1. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from Table 2. In some embodiments, provided is a phosphonic acid ethyl ester of a compound of Table 2. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of Compounds 28-51 in Table 2. In some embodiments, provided is a phosphonic acid ethyl ester of a compound selected from the group consisting of Compounds 28-51 in Table 2. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of Compounds 28-51, 57-125, and 144-168 in Table 2. In some embodiments, provided is a phosphonic acid ethyl ester of a compound selected from the group consisting of Compounds 28-51, 57-125, and 144-168 in Table 2. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of Compounds 28-51, 57-125, 144-168, and 170-305 in Table 2. In some embodiments, provided is a phosphonic acid ethyl ester of a compound selected from the group consisting of Compounds 28-51, 57-125, 144-168, and 170-305 in Table 2. In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of Compounds 28-51, 57-125, 144-168, and 170-547 in Table 2. In some embodiments, provided is a phosphonic acid ethyl ester of a compound selected from the group consisting of Compounds 28-51, 57-125, 144-168, and 170-547 in Table 2.

[0201] Table 1: Representative Compounds of Formula (I), (II), and (III) Co.. Structure NameNo.1 Z zz y— ((R)-2-(5-((lSR,4SR)-4- acetamidocyclohexyl)benzo[b]thiophe \ ne-2-carboxamido)-3 -(3 - / \ £fluorophenyl)propyl)phosphonic acid 2 ((R)-2-(5-((lSR,4RS)-4- 0 « acetamidocyclohexyl)benzo[b]thiophe ne-2-carboxamido)-3 -(3 - ^ O SZ OXT° z s v O o z fluorophenyl)propyl)phosphonic acid b 1“ IIIt / u JL. z..>^' O i'3 HOSOH O Z (R)-(2-(5 -( 1 -acetylpiperidin-4-ZP, CiO1X Cl yl)benzo [b]thiophene -2- °Z7 r-A Or z" carboxamido) -3 -(3 - xO chlorophenyl)propyl)phosphonic acid0Ol f' ' 'Ck X Z o4 11(R)-(2-(5 -( 1 -acetylpiperidin-4- yl)benzo [b]thiophene -2- o<oX cZI carboxamido) -3 -(3 - cyanophenyl)propyl)phosphonic acid K / °O AQ— -- jd) o x°5 rac-(R)-(3-(3-fluorophenyl)-2-(l- r J 6'methyl-4-phenyl-lH-imidazole-2- ^zO zz carboxamido)propyl)phosphonic acid O o--6 OH rac-(R)-(2-( 1 -( 1 -acetylpiperidin-4-yl)-H0'p' 0" i \\ ~ 1 H-pyrazole -3 -carboxamido)-3 -(3 - o / V&i'N \\ / fluorophenyl)propyl)phosphonic acid \ H N-N6, 01°7 (R)-(2-(5 -( 1 -acetylpiperidin-4- ^XXO ^"O yl)benzo [b]thiophene -2- carboxamido) -3 -(3 - °kr'N'O o^. / Ffluorophenyl)propyl)phosphonic acid 1 HOK°H8 rac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl)-2-( 1 -methyl-3 -( 1 - methyl-6-oxo- 1 ,6-dihydropyridin-3 - yl)- 1 H-pyrazole -5 -carboxamido)propyl)phosphonic acidrac-(R)-(2-([ 1 , l'-biphenyl]-4- 0 carboxamido)- 1 , 1 -difluoro-3 -(3- II : F fluorophenyl)propyl)phosphonic acidHO=P-OH[P T OHrac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl)-2-(quinoxaline-2- 0 A^^Fcarboxamido)propyl)phosphonic acid A / 1 Y II N H^V 1 -F> O=P-OHN iOHrac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl)-2-(quinoxaline-6- carboxamido)propyl)phosphonic acid_ rac-(R)-(2-(3-(3-(4-acetylpiperazin-l- yl)phenyl)- 1 -methyl- lH-pyrazole-5- N— > / Kcarboxamido)- 1 , 1 -difluoro-3 -(3- N o x^x^'Ffluorophenyl)propyl)phosphonic acid / =\ A? FJ, H KOHN'NX O^OH> / OH U- rac-(R)-(2-([ 1 , 1 '-biphenyl] -3 - carboxamido)- 1 , 1 -difluoro-3 -(3- ziC fluorophenyl)propyl)phosphonic acid ^V^ oA=H^FO=p-OHOHz z HO, OH rac-(R)-(2-(5-(l-acetylpiperidin-4-ZPXF ClO' ^-F -A yl)benzo [b]thiophene -2- 0 'FAX carboxamido) -3 -(3 -chlorophenyl) -1,1- 1 / — . HN-&\ 7 / / difluoropropyl)phosphonic acid °_ rac-(R)-(2-(3-(3-(l-acetylpiperidin-4- yl)phenyl)- 1 -methyl- lH-pyrazole-5- N— i x"5^carboxamido)- 1 , 1 -difluoro-3 -(3- O f 1( o A^^F fluorophenyl)propyl)phosphonic acid v_ A ’FAAANAK .VA \\ N- 2NXHO. KP.OOHHrac-(R)-(2-(3 -(4-( 1 -acetylpiperidin-4- °^N-K yl)phenyl)- 1 -methyl- lH-pyrazole-5- carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acidN-m^ \ - (7\\HN-< VV&1V'F— \°=Px-ofiFOHrac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl)-2-( 1 -methyl -4-phenyl- lH-imidazole-2- carboxamido)propyl)phosphonic acidOH rac-(R)-( 1 , 1 -difluoro-3 -(3- O=P-OH fluorophenyl)-2-( 1 -methyl-5 -phenyl- lH-imidazole-2- fy-AFcarboxamido)propyl)phosphonic acid ‘W HN^Of-A\ / 3 x> rac-(R)-(2-(5-(l-(3- O aminopropanoyl)piperidin-4- \ O ' a*O O ' yl)benzo [b]thiophene -2- \ x1carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid rac-(R)-( 1 , 1 -difluoro-3 -(3- ofluorophenyl)-2-(4-phenyl-lH- imidazole-2- vO x / » oR xY o fto-u- —uz-' carboxamido)propyl)phosphonic acid7jx / oJ z J \ o' ,\ Z,QrS; x Oi iO ; IL7z CMIA X"rac-(R)-( 1 , 1 -difluoro-3 -(3- nOHO'-'p-OHfluorophenyl)-2-( 1 -methyl-5 -phenyl- YV"-- lH-pyrazole-3- l[ ] ’ / &l Fcarboxamido)propyl)phosphonic acid rHNY° F JTArac-(R)-( 1 , 1 -difluoro-3 -(3- nOH0-^OHfluorophenyl)-2-( 1 -methyl-3 -phenyl- lH-pyrazole-5- { / J ' / &i Fcarboxamido)propyl)phosphonic acid rHNY^° F T1 / N^Zr O>^OHrac-(R)-(2-(lH-benzo[d]imidazole-2- OHcarboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid ioFr _HNJAFz — < xHN^Norac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl)-2-( 1 -methyl- 1H- kwbenzo [d] imidazole -2- X i carboxamido)propyl)phosphonic acid O Xzo Ol / fi / o.A-l oA HOxOH rac-(R)-( 1 , 1 -difluoro-3 -(3 - O='p F fluorophenyl)-2-(3-phenyl-lH- XF / H-^1 0 pyrazole-5- / =< HNA carboxamido)propyl)phosphonic acid M FN\f J(R)-(3-(5-( 1 -acetylpiperidin-4-yl)- 1 - XiO methyl - 1 H-benzo [d] imidazole -2- carboxamido)- 1 , 1 -difluoro-4-(3 - / ° 1■° N A >\nS, _ , _ / Ar N7RT>°W / \ fl ri HcI O fluorophenyl)butyl)phosphonic acid FN ) — fXAN\ / wo \= / F^ 'OHrac-(R)-(2-(5-(l-acetylpiperidin-4- yl)benzo [b]thiophene -2- carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid HN— , (R)-( 1 , 1 -difluoro-3 -(3 -fluorophenyl)- 2-(4-(4-(piperidin-4-yl)pyridin-2- / yl)benzamido)propyl)phosphonic acid —T\\=N \= / HNi,.Z1bsF\=^%CF FHOOH0 rac-((R)-2-((lR,3R)-3-(2-(l- H 0 \ F acetylpiperidin-4-yl)-lH-imidazol-5- / AM V-POaHs yl)cyclobutane - 1 -carboxamido) -1,1- difluoro-3-(3- N-y Hfluorophenyl)propyl)phosphonic acid Frac-(R)-( 1 , 1 -difluoro-3 -(3- Q fluorophenyl)-2-(4-(4-(piperidin- 1 - yl)pyridin-2- yl)benzamido)propyl)phosphonic acid \=N HN— <41F^=\FHO0H(R)-( 1 , 1 -difluoro-3 -(3 -fluorophenyl)- HNyyyyyy yy\ — / X —NX — / HN"-6bsFX — 2-(4-(5-(piperidin-4-yl)pyridin-2- yl)benzamido)propyl)phosphonic acid %CF FHOOH / —T\ rac-(R)-( 1 , 1 -difluoro-3 -(3- \=N \= / HN" <&1F\=\ fluorophenyl)-2-(4-(pyridin-2- yl)benzamido)propyl)phosphonic acid %CF FHO0H0 (rac-(R)-(2-(4-(4-(acetamidomethyl)- 1 H-imidazol -2-yl)benzamido) -1,1- difluoro-3-(3-HH % k fluorophenyl)propyl)phosphonic acid OC0HFFrac ((R)-l,l-difluoro-3-(3- Hhfluorophenyl)-2-((lR,3R)-3-(2- Tl \ / x o, / z / o F. \ / F ! OHK IiI , / / >'" &■2<\z ' / y-p \=o phenyl-lH-imidazol-5-yl)cyclobutane- HN" <&1 OH 1 -carboxamido)propyl)phosphonic acidFF rac-(R)-(2-(5-(l-acetylpiperidin-4- O / ={ yl)benzo [d]thiazole -2-carboxamido) - X^k X^X^N HN—F^- / J1, 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acidHO'pk 'Fo HO' °rac-(R)-(2-(6-( 1 -acetylpiperidin-4- xxO yl)quinazoline-2-carboxamido)- 1 , 1 - difluoro -3 -(3- kk^N'|X''N'k'Z-F fluorophenyl)propyl)phosphonic acid O=P-OHO^NX6H_ ^0 rac-(R)-(2-( 1 -(3 -( 1 -acetylpiperidin-4- yl)phenyl) - 1 H-pyrazole -4- N— \ carboxamido)- 1 , 1 -difluoro-3 -(3- C) IX fluorophenyl)propyl)phosphonic acid . II : F( Nlb^F'N=J O=P-OHOH_ ^O rac-(R)-(2-( 1 -(3 -( 1 -acetylpiperidin-4- yl)phenyl) - 1 H-pyrazole -3 - O carboxamido)- 1 , 1 -difluoro-3 -(3- < O k IX^I'F fluorophenyl)propyl)phosphonic acid N / N<:X^NkV-Fv=AN\kHOXOHOHH rac-((R)- 1 , 1 -difluoro-3 -(3 - f / \ / "'-Z &2 z?F\ / FC 9— N V— PO3H2fluorophenyl)-2-((lR,5S,6S)-3- phenyl-3 -azabicyclo [3.1 ,0]hexane-6- H \ z carboxamido)propyl)phosphonic acid F(R)-(2-(5 -( 1 -acetylpiperidin-4- W J-\ yl)benzo [b]thiophene -2- I \^F ' carboxamido)- 1 , 1 -difluoro-3 -(3-0<XFFfluorophenyl)propyl)phosphonic acid nO HOOHO rac-(R)-(2-(4-(5-acetyl-4, 5,6,7- tetrahydro-lH-imidazo[4,5-c]pyridin-AO:«D^:«GQ 2-yl)benzamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid HZ'0”rac-(R)-(2-(7-(l-acetylpiperidin-4- Z^NZ\yl)imidazo [ 1 ,2-a]pyridine-2- ° S carboxamido)- 1 , 1 -difluoro-3 -(3- N]^\ -Q fluorophenyl)propyl)phosphonic acid HNH2O3PF\j<° rac-(R)-(2-(3'-(l-acetylpiperidin-4-yl)- N [ 1 , 1' -biphenyl] -3 -carboxamido)- 1,1- difluoro-3-(3- 1 Xi fluorophenyl)propyl)phosphonic acid Cl II 11 H51O=P-fOHFOHjQ rac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl)-2-(quinazoline-2- OnrN^^MO=P— OFcarboxamido)propyl)phosphonic acid H OHrac-(R)-(2-(3'-(l-acetylpiperidin-4-yl)- 0 0 r^-^F [ 1 , l'-biphenyl] -4-carboxamido)- 1,1- H II • F difluoro-3-(3- --^N rj^V^N'ai^F fluorophenyl)propyl)phosphonic acidHO=P-OH[[ T 6Hrac-(R)-(2-(5 -(4-acetylpiperazin- 1 -yl)- 1 -methyl - 1 H-benzo [d] imidazole -2- o carboxamido)- 1 , 1 -difluoro-3 -(3- zNV^N^-tFfluorophenyl)propyl)phosphonic acid \ NHP'OHH H / " O*P"OH0 ' — 'x= / 140 rac-(R)-( 1 , 1 -difluoro-3 -(3- fluorophenyl) -2-(quinazoline -7- O carboxamido)propyl)phosphonic acid AA NAAHO=P-OHOH141 o rac-(R)-(2-(4'-( 1 -acetylpiperidin-4-yl)- [ 1 , 1' -biphenyl] -3 -carboxamido)- 1,1-ANIT1 Xi difluoro-3-(3- X XAFfluorophenyl)propyl)phosphonic acid < O=P— OHOH169 (R) -(3 -(benzo [b]thiophene -2- carboxamido)-4-(3- o fluorophenyl)butanoyl)phosphonic XXs. acidQ X' -NHyabs / O~-FH0xioA O OH142 _ rac-(R)-(2-(3-(3-(l-acetyl-4- hydroxypiperidin-4-yl)phenyl)- 1 - N— \ methyl - 1 H-pyrazole -5 -carboxamido) - A-OH o AXAF1, 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid / =\ A4 VAA N 'M?AFF ,N'AOAOH143 rac-(R)-(2-(3 -(2-( 1 -acetylpiperidin-4-O<iX yl)pyrimidin-4-yl)- 1 -methyl- 1H-N— \ pyrazole-5 -carboxamido)- 1,1- difluoro-3-(3- O X XL\ o r ' — fluorophenyl)propyl)phosphonic acid AN _ A A / FN X— / Ar N 4iy-F. .A / v J.HJAHN"NX O^ADH

[0202] Table 2: Representative Compounds of Formula (I), and (IV)Cmpd. Structure and NameNo.28 oX~NHV &^Ao O z;A N lA zv 'y-U 0 A=PX-OHfO OH((R)-2-(5 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid( &iT / =v , —Ko o\ \ 1 H 1 ^OH0N\ ' 0 H ' — H 'x= / / 0*%H((R)-2-(5-(l-(4-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acid OO|Sl £ f- "T o1z*^30HO' OHx / °C\ S / XJ 0 v / ZIrac-((R)-2-(3-(3-(l-(8-(4-(3-((S)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- z^.yl)piperidin- 1 -yl)-8-oxooctanoyl)piperidin-4-yl)phenyl)- 1 -methyl- lH-pyrazole-5- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acido^NHoJ 1 \ II\ rr, x ..Z z lx AWv ' &l / \ / j Y A HNY F \=<N'N NXCX^V YNXJ O=PX-OHF0 OHrac-(R)-(2-(5-(l-(5-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-l-methyl-lH-indazol- 6-yl)pentanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acidHN, &1J. / ?« "NN- s / ? rAJ0X v#n-"s FV VoH / "--i \ \ HO\&3&2\0((R)-2-(5-(l-((lRS,4SR)-4-((l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid((R)-2-(5-((lSR,4SR)-4-(4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro- 1 H-benzo [d] imidazol-5 -yl)methyl)piperidine - 1 - carboxamido)cyclohexyl)benzo[b]thiophene-2-carboxamido)-3-(3- fluorophenyl)propyl)phosphonic acid0YNHQOHN Jk O=p'-OHY i ] > F\((R)-2-(5-(l-(8-(4-(3-((RS)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)piperidin- 1 -yl)-8-oxooctanoyl)piperidin-4-yl)- 1 -methyl- lH-benzo[d]imidazole-2- carboxamido)-3-(3-fluorophenyl)propyl)phosphonic acidoY"NHr> ,x''\A^x''Y / HN-^ / O=\ JI J II J&2 \ / F^-^X O=p.-OH'HOH((R)-2-(5-((lRS,4SR)-4-(4-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)butanamido)cyclohexyl)benzo[b]thiophene-2- carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid0YNHNfXX0OH' I N. x\ x\ A O=p'-OHT i l > Fo HN^\ / =<YA / / \k A / A — A / / ((R)-2-(5-(l-(8-(4-(3-((RS)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)piperidin-l-yl)-8-oxooctanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-3- (3 -fluorophenyl)propyl)phosphonic acidoNH / V&iY° YYN\ / ?- L L -z — \ — \ / N v 'y- O=PX-OHO OH((R)-2-(5 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)-l-methyl-lH-benzo[d]imidazole-2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acido>^NHV&iAo0 QHk N A O=p'~OH T i l > F0ULNMO\((R)-2-(5-(l-(8-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin- 1 -yl)-8-oxooctanoyl)piperidin-4-yl)- 1 -methyl- 1H- benzo[dlimidazole-2-carboxamido)-3-(3-fluorophenyl)propyl)phosphonic acid 0TNHrrW,NTT HN^ \=<o, x; F10 HO0Hrac-((R)-2-(5-(l-(5-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid07“N.HHOSOH< / =° A F F _ o1 \\ °0rac-((R)-2-(5-(l-(8-(4-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-8-oxooctanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acidO,y-nh HO' 'OH<On °"PV TFF T / Frac-((R)-2-(5-(l-(6-(4-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-6-oxohexanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acidW N / —{ zx I HS4LOFHT^NyN^ / Nv_ / \= / °* "OH° NA oH0rac-((R)-2-(5-(l-(4-(4-(l-((R)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4-yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acidH O fF°yNr° 0< &1L / ==\— < ,N"A zrA IHO=P-OH w yzj yOCr °hN o7rac-((R)-2-(5-(l-(4-(4-(l-((R)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acid0ZNHV&ZoXJL" O ?H°„ ,OHO"\p0HN-TZ / =<Y IT _ J.&1\ _ I \Orac-((R)-2-(5-(l-(6-(4-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-6-oxohexanoyl)piperidin-4- yl)benzo [blthiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid°>x / STA JDHSy ZNHo °^ OH° [ JV&t / ^oJ1orac-((R)-2-(5-(l-(8-(4-(3-((R)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)piperidin-l-yl)-8-oxooctanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-3-(3 -fluorophenyl)propyl)phosphonic acid0TjV>NZY T SVN '■= / O ' )=OHN0H°"' / =\0H\_JF((R)-2-(5 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-3- (3 -fluorophenyl)propyl)phosphonic acid_ '-abs0OHCjo 1 / NHf iT1 _ ° J10((R)-2-(5-(l-(8-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin-l-yl)-8-oxooctanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid 0NHo>bSlxF^NICR-OHVN ) — \=N0 ' — '((R)-2-(7 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l-difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid° OHO jT / NHf iVA°T1 _ ° J10rac-((R)-2-(5-(l-(8-(4-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-8-oxooctanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid o AAFAH A JA> 0 Vy0HyNHoAOH / A< / AAN rvANorac-((R)-2-(7-( l-(5-( l-((S)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0A'N'AOA IT TjVAN f A sA A0 )=OHNHOAohAyjFrac-((R)-2-(5-(l-(5-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-3- (3 -fluorophenyl)propyl)phosphonic acidoAT (AW Aow II 1&2 1 HNA / <cF < F(ATI CTO=PA / ((R)-2-(7-((lSR,4RS)-4-(4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- 1 H-benzo [ d] imidazol-5 -yl)methyl)piperidine - 1 -carboxamido)cyclohexyl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3 - fluorophenyl)propyl)phosphonic acid / / ~ \ \ / P\ / — \N\F 2 / ^ \FxJ H n~N> \ &2 / H2O3P^NyL N Wk ” „ JUN 0H O((R)-2-(l-(3-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acid°. / \ JT\ HO,p-OHA H°;VF / &2 \\ \o Y / -XF0NA, °H((R)-2-( 1 -(3 -( 1 -(( 1 RS, 3 SR)-3 -( 1 -((SR)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid£ J HN^ \o. kF'o= / \ N J Xf fHNV "N> / IH0'w y-N o0H0 0^x((R)-2-(6-(l-(5-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)pyrazolo[l,5-a]pyridine-3- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0HN^A0^ 4 \\ I HN^Xp \\F N HO OH0((R)-2-(6-(l-(5-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)pyrazolo[l,5-a]pyridine-3-carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidOr k.2N1X&U M HOOAOHV N— \ H u VF7=\ c&2 \\ 1O ^T\r Y0N HA) °((R)-2-( 1 -(3 -( 1 -(( 1 RS, 3 SR)-3 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid oAT° o A FrlFO=P-OHo(R)-(2-(6-( 1 -(4-(3-(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5-fluoro- 1 -methyl- 1H- indazol-6-yl)cyclohexane- l-carbonyl)piperidin-4-yl)quinoxaline-2-carboxamido)- 1 , 1 - difluoro-3-(3-fluorophenyl)propyl)phosphonic acid0FoNZ / j Y / N^TX JLXMVHO=P-OHOH(R)-(2-(7 -( 1 -(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl-lH- indazol-6-yl)phenyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acid0A NZjT T OHi xi i H°T°Hrac-((R)-2-(7 -( (R) - 1 -(2-(4-(3 -(2,4-dioxotetrahydr Hopyrimidin- 1 (2H)-yl)-5 -fluoro- 1 - methyl- lH-indazol-6-yl)phenyl)acetyl)piperidin-3-yl)quinoxaline-2-carboxamido)- 1,1-difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid' \=7UWN HN^< F^FO ( &2\ HOxYFUHO'^OI lHzo AHN— v L J)°XS1XNZTkNxo((R)-2-(7 -((1 SR,4RS)-4-(3 -( 1 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)piperidin-4- yl)propanamido)cyclohexyl)imidazo [ 1 ,2 -a] pyridine -2-carboxamido) -1,1 -difluoro-3 -(3 - fluorophenyl)propyl)phosphonic acid0YNH F( \=n0JoA 11 AUHO. / A1HO'P-^((R)-2-(l-(3-((l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)oxy)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid0ANHV&IAOA W' IHOF((R)-2-(7-( l-((3-( l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)propoxy)carbonyl)piperidin-4-yl)quinoxaline-2-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0ANH1A° oNAT J 1*5 i 1N°hN H °AOH0(R)-(2-(6-( 1 -(4-((3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)methyl)cyclohexane-l-carbonyl)piperidin-4-yl)quinoxaline-2-carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoVN^° OJL Jx.NOGT^X L JL N A l^s F fHO=P-OHOH(R)-(2-(7 -( 1 -(4-((3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)methyl)cyclohexane-l-carbonyl)piperidin-4-yl)quinoxaline-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid0Z~-\ OHHN. \ „ O=P-QHz-r Li abs / sr- F° N^\ HN— (F / =Z.( / fl 1 &2| 1 1 z) — / \ \N II I&2 1 1 1 N-ZZ y ' — <\ / > / ((R)-2-( 1 -(3-( 1 -(( lRS,4SR)-4-((3 -((RS)-2,6-dioxopiperidin-3-yl)- 1 -methyl- 1H- indazol-6-yl)methyl)cyclohexane- 1 -carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoHr yoYA n 17 OO^N \ - > o N Aab>- / HN—HO=P-OH / \= / OH((R)-2-(7-((lRS,4RS)-4-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-4-yl)butanamido)cyclohexyl)imidazo[l,2-a]pyridine-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0y~NHN^\ / P' n HO0H0((R)-2-(l-(3-((l-((lRS,3SR)-3-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4- yl)oxy)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid0 / NH 0(1 H °O>O °HH / 0((R)-2-(5-(l-((3-(3-((RS)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)propoxy)carbonyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)-l,l-difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0Z"NHHN„.H0W F((R)-2-(7-(l-((lRS,4SR)-4-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4- yl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acid0KNHo=K AAA ( \HN"ZTr \\P oxPF Wi 0f HO X 'OH F t F((R)-2-(7-(l-((lRS,4SR)-4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4- yl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acido=vX n YX X £X H %Ox °O OH((R)-2-( 1 -(3 -(( 1 -(3 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)propanoyl)piperidin-4-yl)oxy)phenyl)-lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0JiHNX o / V= / / N'Av°V0J-l o "abs / / / / HO'P\^FMOHr / F((R)-2-(7-( l-(2-(3-(l-((RS)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)phenyl)-2,2-difluoroacetyl)piperidin-4-yl)imidazo[l,2- alpyridine-2-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid 0y F\^-^rm ii tV&i / ^on='N~r:5::i F ■°^NJUXyy J J J F^P-OH' yJ oF°z'0H((R)-2-(7-( l-(2-(3-(l-((RS)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)phenyl)-2,2-difluoroacetyl)piperidin-4-yl)quinoxaline-2-carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0AT M ° IH0HNhV1kJ XX(R)-(2-(7 -( 1 -(3 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl-lH- indazol-6-yl)phenyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acidoMOHVN^° r^y 'll H °TZXAAANYOFH' u s u(R)-(2-(7 -( 1 -(2-(3 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)phenyl)acetyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l-difluoro-3- (3 -fluorophenyl)propyl)phosphonic acidoHrNv°O^ IN M n °\ \ / , _ , , _ / } V N ''f-F\ / \ / i \ I H 1HN—4^2 &2\— |\A O-P-OH\ — / \= / OH((R)-2-(7-((lRS,4SR)-4-(4-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-4-yl)butanamido)cyclohexyl)imidazo[l,2-a]pyridine-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid' abs / r-T \ \ / "AO=< JHOHNYo o((R)-2-( 1 -(3 -(( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)oxy)phenyl)-lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidO JAKIH / / *\ ' abs / \ / HN^ FX=\N-V^, ' J O- / <FF / 0((R)-2-( 1 -(3 -(( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)oxy)phenyl)-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid00NHC 00<TYZ \ o T -n— / / J II "nO \7 “ T3—- \ / IX • ' < o —? zn( o=\ °OHtf°T°KAZN^YFAJe ° |J Jabs p0Ay / (R)-(2-(4-(5-(4-(2-(4-(3- 0(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-5-fluoro-l-methyl- lH-indazol-6-yl)piperazin- 1 -yl)ethyl)piperidin- 1 -yl)pyridin-2-yl)benzamido)- 1,1- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidA ,0H0 ° abs / k'-’FF / F°< MHN-Z y-Nxo 0((R)-2-(l-(3-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-4-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3-(3- fluorophenyl)propyl)phosphonic acidH0- ,0HANHN^\ IjN— \b5 / =\0&i0o ZX / NZ5' v k0((R)-2-(l-(4-(l-((lR*,4S*)-4-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid((R)-2-(7-( l-(4-(( l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)methyl)piperidine-l-carbonyl)piperidin-4-yl)quinoxaline-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid / =\ / — \ o / N( / H2O3R HN— / ' (FQ0Q ?x°Sr"NHo((R)-2-(7-(l-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)piperidine-l-carbonyl)piperidin-4-yl)quinoxaline-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0KNH1r^NQHI II 'JnO=P-0HyT |abs po AX^F(R)-(2-(4-(4-((4-(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperazin- 1 -yl)piperidin- 1 -yl)methyl)pyridin-2-yl)benzamido)- 1 , 1 - difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidYA — ( N—FJhH / rN> < / ° MNA o((R)-2-( 1 -(3 -( 1 -(4-(( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo [d] imidazol-5 -yl)methyl)piperidine - 1 -carbonyl)piperidin-4-yl)phenyl) - 1 H- pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidH%,OHV ANHN^\ HN °>— <absF / ^= / F0((R)-2-(l-(4-(l-((lR*,4S*)-4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid H z° \ H r TNrH °0 H° 'W I((R)-2-(7 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)quinazoline-2-carboxamido)-l,l- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0CC.C) N~ 4 KHN M 50M VzO / / / HN° Oab®?'"'\;==\HO'F\ Y QOHF7^F((R)-2-( 1 -(3 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)phenyl)-lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid„ H(AYA NtsY' VN / \= / oJ-p / 'FA7 x- / OH° HO((R)-2-(6-(l-(5-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)- 1 , 1 - difluoro-3-(3-fluorophenyl)propyl)phosphonic acid0^-NH / Nzx HNaM F Y / HOOH0((R)-2-(7-(l-((lRS,4SR)-4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4- yl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3 - fluorophenyl)propyl)phosphonic acido , — x\Y o\ / N\HI 1 / ' abs / / - C / V&V^0 HNF((R)-2-(7-( l-(2-(3-(l-((RS)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)phenyl)-2-methylpropanoyl)piperidin-4-yl)imidazo[l,2- a]pyridine-2-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid A XiL 1 l 1nA A / F% AN AAA O=P-OHANNI HN \OHo'(R)-(2-(7 -( 1 -(5 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)- 1 -methyl- lH-indazol-7 - yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acidXxAH / °r H r TNr°A *i\_ HN.\ “T'N J Y ~ abSl Y llA\ o VW0 H0' w I((R)-2-(7 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidAA — ( N—2= / ' — / N— yA H / / ~N> / H2O3PAN\AN' \jA AoFr&K?10SrNHo((R)-2-( 1 -(3 -( 1 -(4-( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)piperidine-l-carbonyl)piperidin-4-yl)phenyl)-lH-pyrazole-4- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidO ANHV&vAo1s A QH0Ol-T F((R)-2-(7 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)quinazoline-2-carboxamido)-l,l- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoy— NHA axtHY1 ° HOOH((R)-2-(7-((l-(5-( l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)amino)imidazo[l,2-a]pyridine-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid0AHAoO^N\=Z o\ \ AabA, / FH tinANx ,N\ ,N<A"OH((R)-2-(7 -(4-(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperazin-l-yl)imidazo[l,2-a]pyridine-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0H / Nr°N-A 7= / \ / PlJI A,7 ° |O^N \ .FNAabA / \ P „ J 'AFW NA V O=P-OHOX fOH((R)-2-(7 -(4-(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperazin-l-yl)imidazo[l,2-a]pyridine-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidrv / AAJ abs>— NH / ^N f l' lT' N j IJP N °H2O3P-A. OF F O T II \ )AAHNAO((R)-2-(l-(2-(4-(2-(4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol-5-yl)methyl)piperidin-l-yl)-2-oxoethyl)-4-hydroxypiperidin-l- yl)pyridin-4-yl) - 1 H-pyrazole -4-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acidA'NH2O3PAF\FO J-A. X.AA N A 0abs\.,,NH\=NVy OH 1 / 1 X AoOAATAHNV0((R)-2-(l-(2-(4-(2-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin- 1 -yl)-2-oxoethyl)-4-hydroxypiperidin- 1 - yl)pyridin-4-yl) - 1 H-pyrazole -4-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acidO-^NI((R)-2-(7-(l-(2-(3-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)quinoxaline-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidOrrFXXX — "A | / X | XX N J] -J fabs_ / TXLJM o F4XOFHOoh((R)-2-(7-(l-((lRS,3RS)-3-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4- yl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acidonF / U^,ZN J O FJX / rFHO "°H((R)-2-(7-(l-((lRS,3RS)-3-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4- yl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acid / =\ / — \ o\ / / &2 \H2O3PXHN— / N\ / UN"Y oH Q((R)-2-(7-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonicacidx xHxrifo- '°HO-^N1((R)-2-(7-(l-(2-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)quinoxaline-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidoV F\ / NHII 1v I I 1HI' Xj IF 6' 'OH((R)-2-(7-(l-(2-(3-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)phenyl)acetyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidHOXX,.,, / ^~Nx- \xN0\\ 4 o \ II ' —0((R)-2-( 1 -(4-( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)phenyl)-lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidN^° n pAA HNay \=(U A HO0Ho'x((R)-2-(7 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)imidazo[l,2-a]pyridine-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidV o\ \_&y01 1 / H'N abs / 'x-FL J °*PC^F / y0Hd OH((R)-2-(7-( l-(2-(3-(l-((RS)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)phenyl)acetyl)piperidin-4-yl)imidazo[l,2-a]pyridine-2-carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid°>0° VF^~NH N=\ / H‘V^F / = / Fjf j o v / 1o((R)-2-( 1 -(4-( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)phenyl)-lH-pyrazole-4- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidHN~ / \\0=< \&1 / >ahsL <HaOaP’^ / ^NH pH — \ J y-Ni-7! L / v — \ • r \^=iFcr X VVNXJ VNvX0o I((R)-2-(7-(4-(2-(4-(l-((RS)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin- 1 -yl)-2-oxoethyl)-4-hydroxypiperidin- 1 - yl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3 - fluorophenyl)propyl)phosphonic acid0f 'NH / fXXXo 9 XvXI p FnJi! 1 N abs\y0X XX / T VN H XFN-CJ IO=P~OH / H60((R)-2-(6-(l-(5-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0bXofloFFypo.H,(R)-(2-(7 -( 1 -(2-(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin- 1 -yl)acetyl)piperidin-4-yl)quinoxaline-2-carboxamido)- 1 , 1 -difluoro-3-(3-fluorophenyl)propyl)phosphonic acidr^NF\ F O . JL JI NabJ* "NH \^NZ7 0o^ / AHN^Z0((R)-2-( 1 -(2-(4-(4-(( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)methyl)piperidine- 1 -carbonyl)piperidin- 1 -yl)pyridin-4-yl)- 1H- pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid CH3N^CH / TN,H2O3P^NyA^N0UX N!^rs V 0 'H ®((R)-2-(l-(3-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acidCkF( i VF0^NHnA ,„ H _ 0 / 0OHOANrac-((R)-2-(3 -(4-( 1 -(4-(4-( 1 -((R)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4-yl)-2- oxopyridin- 1 (2H)-yl)benzamido)- 1 , 1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acidOxHHOXOH / A F F\J2 / __ r'FzPA \ A HN.IKJ-T )1\N~^0rac-((R)-2-(l-(3-(l-(4-(4-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4- yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3-fluorophenyl)propyl)phosphonic acid°V1 r o AAFxX AV A / ? KNH P-0Hv0OH0\ ^ ONC ' —X ' \= / $=Nrac-((R)-2-(7-( l-(4-(4-(l-((R)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4-yl)quinoxaline- 2-carboxamido)- 1 , 1 -difluoro-3 -(3-fluorophenyl)propyl)phosphonic aciduHCV°HAA HN-X / ={V z ~N Y1HN \u<3rac-(R)-(2-(7-(l-(5-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-l-methyl-lH-indazol- 7 -yl)pentanoyl)piperidin-4-yl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 - (3 -fluorophenyl)propyl)phosphonic acidA JkXo=z ' A Jl L A _ N A A 7VA'AA / N-N YA JHO=p-OHOHrac-(R)-(2-(7-(l-(5-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-l-methyl-lH-indazol- 6-yl)pentanoyl)piperidin-4-yl)quinoxaline-2-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acidF.n F O 0°JZFA A NHHO'P'X- / -N N IT6rf2A \AHN / J>° yj74 / NA^ oorac-((R)-2-(3 -( 1 -( 1 -(5 -( 1 -((S)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- lH-benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)-6-oxo-l,6-dihydropyridin-3- yl)benzamido)- 1 , 1 -difluoro-3-(3 -fluorophenyl)propyl)phosphonic acid0OA NA [ Il I 1\ X JJ L AN-N AA ,pNA *1 / NH 0q A«Frac-(R)-(2-( 1 -(4-( 1 -(5-(3-(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)- 1 -methyl- 1H- indazol-6-yl)pentanoyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0X.H HO\ \=O ' -OHX / FZLX / X 1 »A 5"A_norac-((R)-2-( 1 -(3-( 1 -(8-(4-(3-((RS)-2,6-dioxopiperidin-3-yl)- 1 -methyl- lH-indazol-6-yl) piperidin-l-yl)-8-oxooctanoyl) piperidin-4-yl) phenyl)- lH-pyrazole-4-carboxamido)- l,l-difluoro-3 -(3 -fluorophenyl) propyl) phosphonic acid0HOAOH1Irac-((R)-2-( 1 -(4-( 1 -(5 -( 1 -((R)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 -dihydro- 1 H-benzo [d] imidazol-5 -yl)pentanoyl)piperidin-4-yl)phenyl) - 1 H-pyrazole -4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0XNHHOyOHo'" V-FFN^VVX / VN-J N^ / 'O10rac-((R)-2-( 1 -(3 -( 1 -(5 -( 1 -((R)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 -dihydro- 1 H-benzo [d] imidazol-5 -yl)pentanoyl)piperidin-4-yl)phenyl) - 1 H-pyrazole -4- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid0Z^NHO0O,&2XVFFVP.FFHO' OHrac-((R)-2-(7 -( 1 -(5 -( 1 -((R)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)imidazo[l,2-a]pyridine-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidooHN-X L Ji Z SOYYY \^N X° / XHNH0' O 'THFFOFrac-((R)-2-(5-(l-(l-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidine-4-carbonyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid0<NH / \ &1Z^O .0 r, — a.i £ T / M 7 / ''y^ / kN HN-V F =\° N 'y sz O=PX-OHFO OHrac-((R)-2-(5-(l-(2-(3-(l-((R)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol-5-yl)phenyl)acetyl)piperidin-4-yl)-l-methyl-lH- benzo [d] imidazole -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acid« A-WVN L IL / / — \ *2 / — \ / / >0 / WA / ^ HN^P\=<\ *1 / _ _ I FN A\ / M ? T ,%H1 JA / \A0HOOH0"^N1rac-((R)-2-(5-(l-(2-(3-(l-((R)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol-5-yl)- IH-pyrazol- 1 -yl)acetyl)piperidin-4-yl)- 1 -methyl- 1H- benzo [d] imidazole -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acidZP f J0\^~ / — \ ° A AAA / ( ' / \ 11 : FrM-OHHO((R)-2-(5-(l-(4-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-4-yl)piperidin-l-yl)-4-oxobutanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acid0 C ,NHaw"' A0 HO'OH((R)-2-(5-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)benzo [blthiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acidI M0°N' OHnXH°^°H((R)-2-(5 -( 1 -(5 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-4-yl)pentanoyl)piperidin-4-yl)-l-methyl-lH-benzo[d]imidazole-2-carboxamido)-3-(3-fluorophenyl)propyl)phosphonic acido HyNv° AAx ®rt 1 / - \ / - X O Orac-((R)-2-(5-(l-(4-(4-(l-((R)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin- 1 -yl)-4-oxobutanoyl)piperidin-4-yl)- 1 -methyl - IH-benzo [d]imidazole-2-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acidVNx^° A Arac-((R)-2-(5-(l-(4-(4-(3-((S)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)piperidin- 1 -yl)-4-oxobutanoyl)piperidin-4-yl)- 1 -methyl- lH-benzo[d]imidazole-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidO<NH / \ Ao .0 xA £ I H AA ) °V XA J OA >1o HO0Hrac-((R)-2-(5-(l-(5-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)pentanoyl)piperidin-4-yl)-l-methyl-lH-benzo[d]imidazole-2- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidj?HVOH[""ATA O \1 &2 / / F. L L II / / / H O I J\\ / N-N^((R)-2-(5-(l-((lRS,4RS)-4-((4-(3-((SR)-2,6-dioxopiperidin-3-yl)-l-methyl-lH- indazol-6-yl)piperidine- 1 -carbonyl)oxy)cyclohexane- 1 -carbonyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid 1HV0H[A ' LA ° ) 79 Tr IT / abs\ / \z. 1 L IL )~ \ \ / / XTN-N^((R)-2-(5 -( 1 -(( 1 RS,4RS)-4-((4-(3 -((RS)-2,6-dioxopiperidin-3 -yl)- 1 -methyl- 1H- indazol-6-yl)piperidine- 1 -carbonyl)oxy)cyclohexane- 1 -carbonyl)piperidin-4-yl)benzo [b]thiophene -2-carboxamido) -3 -(3 -fluorophenyl)propyl)phosphonic acid0(NH / \ £ L M r \ )N J 1 J. J VF\-x / O=PXF' o HO OHrac-((R)-2-(5 -( 1 -(5 -(3 -((R)-2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-6- yl)pentanoyl)piperidin-4-yl)- 1 -methyl- lH-benzo[d]imidazole-2-carboxamido)- 1 , 1- difluoro-3-(3-fluorophenyl)propyl)phosphonic acid0>^NHNO£19H9 ,OHLxN^x^x-^x^ANxy0ZVF F° HN— 42F / =(£. X #\rac-((R)-2-(5-(l-(8-(4-(3-((R)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)piperidin- 1 -yl)-8-oxooctanoyl)piperidin-4-yl)- 1 -methyl- lH-benzo[d]imidazole-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0<NH / \ &l / =O xZ\^N ,0v N U x / w x_x vU x / O=PX / -OHfO OH((R)-2-(5-(l-(5-(3-((RS)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)pentanoyl)piperidin-4-yl)-l-methyl-lH-benzo[d]imidazole-2-carboxamido)-3-(3- fluorophenyl)propyl)phosphonic acidv T£o s< o ii “J,, 7N-"% / / \ _ / \ y / — \ T10-P=0y-N ) X—yxOHO^N \-Jrac-((R)-2-(5-(l-(4-(4-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro- lH-benzo[d]imidazol-5-yl)piperidin- 1 -yl)-4-oxobutanoyl)piperidin-4-yl)- 1 -methyl- IH-benzo [d]imidazole-2-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acidOX-NHX NX xXz X^xxXx- xx^J xx_J / O=PXZ-OFHF0 OHrac-((R)-2-(5-(l-(5-(3-((S)-2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6- yl)pentanoyl)piperidin-4-yl)benzo [b]thiophene-2-carboxamido)- 1 , 1 -difluoro-3 -(3-fluorophenyl)propyl)phosphonic acidOP^-NH,0 r. — A* JL H > <10 7 o.x >1O HOOHrac-((R)-2-(5-(l-(3-(l-((S)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)propanoyl)piperidin-4-yl)benzo[b]thiophene-2-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0>-NHHO OHoO=PVFFN~ / \ u rF r- ( i X / N'Z Z y A yz —o y / s((R)-2-(5-(l-(8-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin-l-yl)-8-oxooctanoyl)piperidin-4- yl)benzo [b]thiophene -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acidL ChA OA 7-NH ZHXP,o=c JT 'X0°h' ^ o°nN'N0((R)-2-( 1 -(3 -(( 1 -( 1 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)azetidine-3-carbonyl)piperidin-4-yl)oxy)phenyl)-3-methyl-lH- pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acido ) — / V~~NH / \F| / cF\ 0abs / "'\ JDHV^Ao VNHn'A\ J O OHo=Nz=\4 11 1 x^ O x-s. N Z~Meo((R)-2-(l-(3-((l-((lRS,3SR)-3-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4- yl)oxy)phenyl)-4-methyl-lH-pyrazole-3-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acido C ) —A 'Z V^NH / \ F l / cF( C Oabs / ""\ ,OH\ J 'VNH °.A OHo((R)-2-(l-(3-((l-((lRS,3SR)-3-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4-yl)oxy)-2- fluorophenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid O / \N— >0 H ANZXY°V V rrJ. HNib%^f V\I &1 J / ) '- I- / Vs AANHOOH° \((R)-2-( 1 -(3 -(( 1 -(3 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo [d] imidazol-5 -yl)phenyl)piperidin-4-yl)oxy)phenyl) - 1 H-pyrazole -4- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acido2^NHXAoow °o^NX JI / \ 1 ii jA ri / nAH°=toH / Y j5Tn((R)-2-(7-((l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)oxy)quinoxaline-2-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid0?-NH0 rj^i°5X\NU((R)-2-(7 -( 1 -( 1 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazole-5-carbonyl)piperidine-4-carbonyl)piperidin-4-yl)quinoxaline-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid((R)-2-(7 -(( 1 R* ,4R* )-4-(4-(( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro- 1 H-benzo [d] imidazol-5 -yl)methyl)piperidine - 1 - carbonyl)cyclohexyl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acid0A-NH°AW M ftW ,cr "OH((R)-2-(7-((lR*,4S*)-4-(4-((l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro- 1 H-benzo [d] imidazol-5 -yl)methyl)piperidine - 1 - carbonyl)cyclohexyl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acid0ANHo rj^iN I AFL JUHp'°Hcr "OH((R)-2-(7-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4- yl)quinoline-2-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid Q ANHMA JIA A NlAlA AAT M ft N^FMV O=P-OHOH((R)-2-(7 -( 1 -(( 1 RS, 3 SR)-3 -((1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclobutane-l-carbonyl)piperidin-4- yl)quinoxaline -2-carboxamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acid0A-NH0 fj^A T'FL JI JHP'°O'" "OHH((R)-2-(6-(l-((lRS,4SR)-4-((l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclohexane-l-carbonyl)piperidin-4-yl)quinoline-3 -carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid0 / —> OHHW0 0=P5?10\F / ==(F°=( T II 1 \ < / ) / ((R)-2-( 1 -(3 -( 1 -(4-(( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)methyl)piperidine-l-carbonyl)piperidin-4-yl)phenyl)-3-methyl- lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid 0KNHv ' abs / \ / U j "v J p0((R)-2-(l-(3-((l-((lRS,3SR)-3-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4- yl)oxy)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acid0XNHVyj / ^o°X Jl J OH / N^ T X HI H°TOHXj I R j((R)-2-(3'-(4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin- 1 -yl)-[ 1 , 1 '-biphenyl] -3-carboxamido)- 1 , 1 -difluoro-3- (3 -fluorophenyl)propyl)phosphonic acid0Z"NHCXo pXF0=\ k 11 9 VKN%p|bs4 V'F°H_ _ / o*P\'OH((R)-2-(3-(4-((4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin- 1 -yl)methyl)- IH-pyrazol- 1 -yl)benzamido)- 1,1- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoXNHi OHHO=XOH' UN JU J TUFlj((R)-2-(4'-((4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo [d] imidazol-5 -yl)piperidin- 1 -yl)methyl) -[1,1' -biphenyl] -3 -carboxamido) -1,1- difluoro-3-(3-fluorophenyl)propyl)phosphonic acidoZ~NHUJJwG AZ|| N absV— FHo=p-OHOH((R)-2-(3'-((4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo [d] imidazol-5 -yl)piperidin- 1 -yl)methyl) -[1,1' -biphenyl] -3 -carboxamido) -1,1- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0 QGY / Y VA°1XX ZZ- UJY-y .^3HNYF^F / Z—■ °<FHO °H((R)-2-(l-(3-((4-( l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperazin-l-yl)methyl)phenyl)-3-methyl-lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0 J / \ TIZ / Y J5~NHXX L Y JL o O."XHNXFF°XFHO °H((R)-2-(l-(3-(((lRS,4SR)-4-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexyl)oxy)phenyl)-3-methyl-lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid((R)-2-(l-(3-((4-( l-((RS)-2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo [d] imidazol-5 -yl)piperidin- 1 -yl)methyl)phenyl) -3 -methyl- 1 H-pyrazole -4- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acido<NHJYA n : FH°=F°H' VJUOH((R)-2-(4'-((4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo [d] imidazol-5 -yl)piperidin- 1 -yl)methyl) -[1,1' -biphenyl] -4-carboxamido) -1,1- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidOHO~pf'OH0 / ~NH VNH ITj-n n CVY"-» / H((R)-2-( 1 -(3 -( 1 -(4-(( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)amino)piperidine-l-carbonyl)piperidin-4-yl)phenyl)-lH- pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid 0^-NHn 1 HN—CX=<o=\ JL rY » i vF\NJ 0* AF5^ HO "0H((R)-2-(l-(3-((l-((lRS,3SR)-3-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)azetidin-3-yl)oxy)phenyl)- lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid 0NOLI1\zNV / \N H a°bsTA—0FHNY T F°((R)-2-(6-((lSR,4RS)-4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-5-fluoro-l- methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)quinoxaline-2-carboxamido)- 1,1-difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0ANH° 2<^ °HV°= I 11Hr^N - - uMa"bS / VTFF' L N XN^f ' V ' 3 o ~O=<((R)-2-(4-(4-((4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)piperidin- 1 -yl)methyl)- IH-pyrazol- 1 -yl)benzamido)- 1,1- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoy-NHVayAo' UJA . ?hi H °=yAoHJ-k w abs4— FT i Fo Ax / FXj((R)-2-(3'-((4-(l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo [d] imidazol-5 -yl)piperidin- 1 -yl)methyl) -[1,1' -biphenyl] -4-carboxamido) -1,1- difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoAHyo / XX VNOXXXLZ0N \HN5^ \ yVJ / o, XF AZzF\ F FHO OH((R)-2-(7 -( 1 -( 1 -(3 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo [d] imidazol-5 -yl)phenyl)cyclopropane - 1 -carbonyl)piperidin-4-yl) -3 - methylimidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3- fluorophenyl)propyl)phosphonic acidoANH\__&yXo7NZ HNAXF ^J CF3O AFHOOH((R)-2-( 1 -(3 -( 1 -( 1 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H- benzo[d]imidazol-5-yl)azetidine-3-carbonyl)piperidin-4-yl)phenyl)-3- (trifluoromethyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3-fluorophenyl)propyl)phosphonic acido Cfp&2 \ 1 1 I KI— / N H"aTbs\Az S FV<zN^ HOXn , ohO HO((R)-2-(l-(3-(l-((lRS,3SR)-3-((l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)methyl)cyclobutane-l-carbonyl)piperidin-4- yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3-(3- fluorophenyl)propyl)phosphonic acidV _ oZ~NH X"N"VX / H O^F / DJ °((R)-2-(7-((lRS,4SR)-4-((3-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro- 1 H-benzo [d] imidazol-5 -yl)phenyl)carbamoyl)cyclohexyl)imidazo [1,2- alpyridine-2-carboxamido)-l,l-difluoro-3-(3-fluorophenyl)propyl)phosphonic acid 0T z57WN=,H°T° O^~N\U k ^F0LX((R)-2-(l-(3-(l-((lRS,4SR)-4-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid o / ^NHl &lXn ° H JOp'OH / H°b'V2D X^NDNTFZFl _ 1&2 / 1—O((R)-2-( 1 -(4-( 1 -(( 1 RS, 3 SR)-3 -( 1 -((SR)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4-yl)phenyl)-4- methyl- 1 H-pyrazole -3 -carboxamido) -1,1 -difluoro -3 -(3 - fluorophenyl)propyl)phosphonic acidH°. ,OHO0abs / k^FF / F< |&^2 J\ 1 1 Z\ / NDOu°=(HN— \^NxO O((R)-2-( 1 -(3 -( 1 -(( 1 RS,4SR)-4-( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)cyclohexane-l-carbonyl)piperidin-4-yl)phenyl)- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acid OHHnr i H°T°H_ zNA .A A H YI T k ,N’ . .N ' A \ 0 n Y FY YY YN° YYoz x((R)-2-(7-( l-(4-(( l-((RS)-2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH- benzo[d]imidazol-5-yl)amino)piperidine-l-carbonyl)piperidin-4-yl)quinoxaline-2- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidoY A oA ^^FY J JIH,°'p' OOHH / f l N =\ / HN °Y VF / YXVMH o. 'n YnJ(R)-(2-( 1 -(3 -( 1 -(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)phenyl)piperidin-4-yl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidOY-NHCcxL .CL O YA°YFHO °H((R)-2-( 1 -(3-(( 1 S* ,4R*)-4-((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5-fluoro- 1 - methyl- lH-indazol-6-yl)piperidin- 1 -yl)methyl)cyclohexyl)phenyl)-3-methyl- 1H- pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid oY-NHYN^0NYCXC XX o YAFHO °H((R)-2-( 1 -(3-(( 1 S* ,4S*)-4-((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5-fluoro- 1 - methyl- lH-indazol-6-yl)piperidin- 1 -yl)methyl)cyclohexyl)phenyl)-3-methyl- 1H-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidoN\ HrAPf .HJN= / HN^X F^F' LJXO^-p' FHO '°H(R)-(2-( 1 -(3 -( 1 -(3 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)phenyl)piperidin-4-yl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acido / =\C~NH V-X~FV. C=ON o Z LF-FkrV KNJF?P-OHN II A N=< G' \u(R)-(2-(7 -(4-((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin- 1 -yl)methyl)- IH-pyrazol- 1 -yl)quinoxaline-2-carboxamido)- 1 , 1 - difluoro-3-(3-fluorophenyl)propyl)phosphonic acidOte c, r — Uk Hiate / 'F F7L N XHV tte' \ O(R)-(2-(4-(4-((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin- 1 -yl)methyl)- IH-pyrazol- 1 -yl)-2-methylbenzamido)- 1 , 1 - difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidO ANHN^XYF / f CJorl |I orlj / "M M HN-\ 4c\=)<abs\ \O< XFFp,HO'OH((R)-2-(4-(4-(( IS* ,4R*)-4-(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 - methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)- IH-pyrazol- 1 -yl)-2-methylbenzamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acid0ANHCrr / l ^l|or1 |I or1J / / =< 0 z—VNA r \ ?- / / N HN^VFM0^ XFfHOAOH((R)-2-(4-(4-((lS*,4S*)-4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-5-fluoro-l- methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)- IH-pyrazol- 1 -yl)-2- methylbenzamido) -1,1 -difluoro -3 -(3 -fluorophenyl)propyl)phosphonic acid oVN>XXF' LJv | / or1X ]1 orljCL N / ? . — \ 7F^F°< / OFHHO((R)-2-( 1 -(4-(( IS* ,4R*)-4-(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 - methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)phenyl)-3-methyl- lH-pyrazole-4- carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0?^NHV -^0CcC7|or1ILorCp / TAI / X ? \s=ZN^= / \ absX / F1V F°< / PC OFHHO((R)-2-(l-(4-((lS*,4S*)-4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-5- fluoro- 1 -methyl- lH-indazol-6-yl)piperi din- 1 -yl)cyclohexyl)phenyl)-3 -methyl- lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluor opheny l)propy l)pho sphoni c aci do^>0kZFN HNryjA S^F^F°<PCFHO °H(R)-(2-( 1 -(4-( 1 -(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)phenyl)piperidin-4-yl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidH?P-OH° / ° VFANH\_j / NV >=O / t II °<X~Y(R)-(2-( 1 -(4-( 1 -(3 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)phenyl)piperidin-4-yl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid1 NHV&p^o \ I,Fy Vb8'"'V0H7-NH^P\JT 10°huN0((R)-2-(l-(3-((l-((lRS,3SR)-3-(l-((SR)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-5-yl)cyclobutane-l-carbonyl)piperidin-4- yl)oxy)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)-l,l-difluoro-3-(3- fluorophenyl)propyl)phosphonic acidoAH_ ,CI / NXX \ _ _ V I N \^JT^’ NX \0 / ftAA F WZP\ FHO OH F((R)-2-(3 -chloro-7 -( 1 -(2-(3 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)phenyl)-2,2-difluoroacetyl)piperidin-4- yl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0AH^0 / =\ / ClN—\ J V k / °o. vFZP\ F FHO OH((R)-2-(3 -chloro-7 -( 1 -( 1 -(3 -( 1 -((RS)-2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3 - dihydro-lH-benzo[d]imidazol-5-yl)phenyl)cyclopropane-l-carbonyl)piperidin-4- yl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3 - fluorophenyl)propyl)phosphonic acid0ANA NACAXX / X1&2| / =\A A „ OHN)^NHV<OHo / VF< FAvF((R)-2-(3 -(4-(( 1 SR,4SR)-4-(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 - methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)- IH-pyrazol- 1 -yl)benzamido)- 1, 1 - difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidA oNtCA >h / T \ ^N 1 / J / 0abs / V^i—FFHzNvF / =v'U0((R)-2-(l-(3-((lS*,4S*)-4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-5-fluoro-l- methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)phenyl)-3-methyl- lH-pyrazole-4-carboxamido) -1,1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid0CNAo< JI IOHO^OHmNTF / = / XJ0((R)-2-( 1 -(3 -(( 1 S * ,4R*)-4-(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 - methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclohexyl)phenyl)-3-methyl- lH-pyrazole-4- carboxamido)- 1 , 1 -difluoro-3 -( 3 -fluorophenyl)propyl)phosphonic acidO HO AT / j CT °1"’pv° \ \ 7 i -o / r LL --F / =<F\ Oi n o. V z °ViO O' '((R)-2-(l-(4-((lSR,4SR)-4-((4-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-5-fluoro-l- methyl- lH-indazol-6-yl)piperidin- 1 -yl)methyl)cyclohexyl)phenyl)-3-methyl- 1H- pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid 0p\ / o _ / r z°<FHO °H(R)-(2-( 1 -(3 -((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin-l-yl)methyl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acidopV , F / / ° a"bs / V^rF- FN J JL M'^ 3XJT °(R)-(2-( 1 -(4-((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin-l-yl)methyl)phenyl)-3-methyl-lH-pyrazole-4-carboxamido)- 1 , 1 -difluoro-3 -(3 -fluorophenyl)propyl)phosphonic acid(R)-(2-(3 -((4-((4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin- 1 -yl)methyl)piperidin- 1 -yl)methyl)-7 -(2 -oxo- 1 ,3 -oxazinan-3 - yl)imidazo [ 1 ,2-a]pyridine-2-carboxamido)- 1 , 1 -difluoro-3 -(3 - fluorophenyl)propyl)phosphonic acidoN HO'P'OH1 / °"' XNA / 'yx HNSTF / I _ / \XJ °(R)-(2-( 1 -(3 -(4-(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)-5 -fluoro- 1 -methyl- 1H- indazol-6-yl)piperidin- 1 -yl)phenyl) -3 ...

Claims

CLAIMSWhat is claimed is:

1. A compound of Formula (I):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla, 6- to 10-membered aryl optionally substituted with one or more Rla, 4- to 12-membered heterocyclyl optionally substituted with one or more Rlb, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb;Ring 2 is phenyl optionally substituted with one or more R2a, 5- to 6-membered heteroaryl optionally substituted with one or more R2a, or 4- to 12-membered heterocyclyl optionally substituted with one or more R2b;R1and R2are each independently H or F, orR1and R2are taken together to form oxo, orR1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl;R3, R4, and R5are each independently H or Ci-4alkyl;m is 0 or 1;Q is absent or is Ring 3,wherein Ring 3 is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, 6- to 10-membered aryl optionally substituted with one or more R3a, 3- to 8- membered cycloalkyl optionally substituted with one or more R3b, or 4- to 12- membered heterocyclyl optionally substituted with one or more R3b;or Q is of formula (i):Linker — { Dwherein:Ring A is selected from the group consisting of:optionally substituted with one or more groups independently selected from Ci-4alkyl and halo;X is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, -or -N(Ry)C(0)-;Ring B is selected from the group consisting of:optionally substituted with one or more groups independently selected from halo, Ci- 4alkyl, Ci-4haloalkyl, or OH; wherein RBis H or Ci-4alkyl, and wherein # indicates attachment to X;W is a bond, -O-, -CH2-, -N(Ry)-, -C(0)N(Ry)-, or -N(Ry)C(0)-;Ring C is optional, wherein W is a bond when Ring C is absent, and when Ring C is present, Ring C is 4- to 12-membered heterocyclyl optionally substituted with one or more Rc, 3- to 8-membered cycloalkyl optionally substituted with one or more Rc, 6- to 10-membered aryl optionally substituted with one or more RCa, or 5- to 10-membered heteroaryl optionally substituted with one or more RCa;Linker is a bond, -O-, -C(O)-, -N(Ry)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, - OC(O), Ci-ioalkylene, C(0)Ci-ioalkylene, Ci-ioalkyleneC(O), C(0)Ci-ioalkyleneC(0), Ci-ioalkyleneC(0)Ci-ioalkylene, -C2alkynylene-, -C2alkynylene-Ci-ioalkylene, Ci-ioalkylene-C2alkynylene-, -C2alkynylene-Ci-ioalkylene-C2alkynylene-, Ci-ioalkylene-C2alkynylene-Ci-ioalkylene, -N(Ry)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)-, -N(Ry)-Ci-ioalkylene-N(Ry)-, Ci-ioalkylene-N(Ry)-Ci-ioalkylene, -O-Ci-ioalkylene, Ci-ioalkylene-0-, -O-Ci-ioalkylene-O-, Ci-ioalkylene-O-Ci-ioalkylene, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -C(0)N(Ry)-Ci-ioalkylene-C(0)N(Ry)-, Ci-ioalkylene-C(0)N(Ry)-Ci-ioalkylene, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, -N(Ry)C(0)-Ci-ioalkylene-N(Ry)C(0)-, Ci-ioalkylene-N(Ry)C(0)-Ci-ioalkylene, C(0)0-Ci-ioalkylene, Ci-ioalkyleneC(O)©-, C(0)0-Ci-ioalkyleneC(0)0-, Ci- ioalkyleneC(0)0-Ci-ioalkylene, -OC(0)Ci-ioalkylene, Ci-ioalkylene-OC(O), -OC(0)Ci-ioalkylene-OC(0), Ci-ioalkylene-OC(0)Ci-ioalkylene, 6- to 10-membered arylene, -(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-Ci-ioalkylene-(6- to 10-membered arylene)-, Ci-ioalkylene-(6- to 10-membered arylene)-Ci-ioalkylene, 5- to 10-membered heteroarylene, -(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-Ci-ioalkylene-(5- to 10-membered heteroarylene)-, Ci-ioalkylene-(5- to 10-membered heteroarylene)-Ci-ioalkylene, 4- to 12-membered heterocyclylene, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-Ci-ioalkylene-(4- to 12-membered heterocyclylene)-, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-© i-walkylene, 3- to 8-membered cycloalkylene, -(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-Ci-ioalkylene-(3- to 8-membered cycloalkylene)-, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, -(6- to 10-membered arylene)-O-, -O-(6-to 10-membered arylene)-, -(6- to 10-membered arylene)-O-(6- to 10-membered arylene)-, -O-(6- to 10-membered arylene)-O-, -(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-O-(5- to 10-membered heteroarylene)-, -O-(5- to 10-membered heteroarylene)-O-, -(4-to 12-membered heterocyclylene)-©-, -O-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-O-(4- to 12-membered heterocyclylene)-, -O-(4- to 12-membered heterocyclylene)-©-, -(3- to 8-membered cycloalkylene)-©-, -O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-O-(3- to 8-membered cycloalkylene)-, -O-(3- to 8-membered cycloalkylene)-©-, -(6- to 10-membered arylene)-C(O)-, -C(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)-(6- to 10-membered arylene)-, -C(O)-(6- to 10-membered arylene)-C(O)-, -(5- to 10-membered heteroarylene)-C(O)-, -C(O)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)-(5- to 10-membered heteroarylene)-, -C(O)-(5- to 10-membered heteroarylene)-C(O)-, -(4- to 12-membered heterocyclylene)-C(O)-, -C(O)-(4- to 12-membered heterocyclylene)-, -(4-to 12-membered heterocyclylene)-C(O)-(4- to 12-membered heterocyclylene)-, -C(O)-(4- to 12-membered heterocyclylene)-C(O)-, -(3- to 8-membered cycloalkylene)-C(O)-, -C(O)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)-(3- to 8-membered cycloalkylene)-, -C(O)-(3- to 8-membered cycloalkylene)-C(O)-, -(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)-(6- to 10-membered arylene)-, -N(Ry)-(6- to 10-membered arylene)-N(Ry)-, -(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)-(5- to 10-membered heteroarylene)-, -N(Ry)-(5- to 10-membered heteroarylene)-N(Ry)-, -(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)-(4- to 12-membered heterocyclylene)-, -N(Ry)-(4- to 12-membered heterocyclylene)-N(Ry)-, -(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)-(3- to 8-membered cycloalkylene)-, -N(Ry)-(3- to 8-membered cycloalkylene)-N(Ry)-, -(6- to 10-membered arylene)-C(O)N(Ry)-, -C(0)N(Ry)-(6- to 10-membered arylene)-, -(6-to 10-membered arylene)-C(0)N(Ry)-(6- to 10-membered arylene)-, -C(0)N(Ry)-(6-to 10-membered arylene)-C(O)N(Ry)-, -(5- to 10-membered heteroarylene)-C(0)N(Ry)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)N(Ry)-(5- to 10-membered heteroarylene)-, -C(0)N(Ry)-(5- to 10-membered heteroarylene)-C(O)N(Ry)-, -(4- to 12-membered heterocyclylene)-C(0)N(Ry)-, -C(0)N(Ry)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)N(Ry)-(4- to 12-membered heterocyclylene)-, -C(0)N(Ry)-(4-to 12-membered heterocyclylene)-C(O)N(Ry)-, -(3- to 8-membered cycloalkylene)-C(0)N(Ry)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)N(Ry)-(3- to 8-membered cycloalkylene)-, -C(0)N(Ry)-(3- to 8-membered cycloalkylene)-C(O)N(Ry)-, -(6- to 10-membered arylene)-N(Ry)C(O)-, -N(Ry)C(0)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-N(Ry)C(O)-(6- to 10-membered arylene)-, -N(Ry)C(0)-(6- to 10-membered arylene)-N(Ry)C(O)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-N(Ry)C(O)-(5- to 10-membered heteroarylene)-, -N(Ry)C(0)-(5- to 10-membered heteroarylene)-N(Ry)C(O)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-N(Ry)C(O)-(4- to 12-membered heterocyclylene)-, -N(Ry)C(0)-(4- to 12-membered heterocyclylene)-N(Ry)C(0)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-N(Ry)C(O)-(3- to 8-membered cycloalkylene)-, -N(Ry)C(0)-(3- to 8-membered cycloalkylene)-N(Ry)C(0)-, -(6- to 10-membered arylene)-C(O)O-, -C(O)O-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-C(O)O-(6- to 10-membered arylene)-, -C(O)O-(6- to 10-membered arylene)-C(O)O-, -(5- to 10-membered heteroarylene)-C(O)O-, -C(O)O-(5- to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-C(O)O-(5- to 10-membered heteroarylene)-, -C(O)O-(5- to 10-membered heteroarylene)-C(O)O-, -(4- to 12-membered heterocyclylene)-C(O)O-, -C(O)O-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-C(O)O-(4- to 12-membered heterocyclylene)-, -C(O)O-(4- to 12-membered heterocyclylene)-C(O)O-, -(3- to 8-membered cycloalkylene)-C(O)O-, -C(O)O-(3- to 8-membered cycloalkylene)-, -(3- to 8-membered cycloalkylene)-C(O)O-(3- to 8-membered cycloalkylene)-, -C(O)O-(3- to 8-membered cycloalkylene)-C(O)O-, -(6-to 10-membered arylene)-OC(O)-, -OC(O)-(6- to 10-membered arylene)-, -(6- to 10-membered arylene)-OC(O)-(6- to 10-membered arylene)-, -OC(O)-(6- to 10-membered arylene)-OC(O)-, -(5- to 10-membered heteroarylene)-OC(O)-, -OC(O)-(5-to 10-membered heteroarylene)-, -(5- to 10-membered heteroarylene)-OC(O)-(5- to 10-membered heteroarylene)-, -OC(O)-(5- to 10-membered heteroarylene)-OC(O)-, -(4- to 12-membered heterocyclylene)-OC(O)-, -OC(O)-(4- to 12-membered heterocyclylene)-, -(4- to 12-membered heterocyclylene)-OC(O)-(4- to 12-membered heterocyclylene)-, -OC(O)-(4- to 12-membered heterocyclylene)-OC(O)-, -(3- to 8-membered cycloalkylene)-OC(O)-, -OC(O)-(3- to 8-membered cycloalkylene)-, -(3-to 8-membered cycloalkylene)-OC(O)-(3- to 8-membered cycloalkylene)-, -OC(O)-(3- to 8-membered cycloalkylene)-OC(O)-, Ci-ioalkylene-(6- to 10-memberedarylene)-O-, -O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O), C(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)-, -N(Ry)-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)C(O)N(Ry)-, C(0)N(Ry)-(6-to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-N(Ry)C(0), -N(Ry)C(0)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6-to 10-membered arylene)C(O)O-, C(O)O-(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(6- to 10-membered arylene)-OC(O), -OC(O)(6- to 10-membered arylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-O-, -O-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroaryl ene)C(O), C(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)-, -N(Ry)-(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)N(Ry)-, C(0)N(Ry)-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-N(Ry)C(O), -N(Ry)C(0)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)C(O)O-, C(O)O-(5- to 10-membered heteroarylene)-Ci-walkylene, Ci-ioalkylene-(5- to 10-membered heteroarylene)-OC(O), -OC(O)(5- to 10-membered heteroarylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-O-, -O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O), C(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)-, -N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4-to 12-membered heterocyclylene)C(O)N(Ry)-, C(0)N(Ry)-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-N(Ry)C(0), -N(Ry)C(0)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)C(O)O-, C(O)O-(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(4- to 12-membered heterocyclylene)-OC(O), -OC(O)(4- to 12-membered heterocyclylene)-Ci-ioalkylene, Ci-ioalkylene-(3-to 8-membered cycloalkylene)-O-, -O-(3- to 8-membered cycloalkylene)-Ci-walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O), C(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)-, -N(Ry)-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)N(Ry)-, C(0)N(Ry)-(3- to 8- membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-N(Ry)C(O), -N(Ry)C(0)(3- to 8-membered cycloalkylene)-Ci- walkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)C(O)O-, C(O)O-(3- to 8- membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-(3- to 8-membered cycloalkylene)-OC(O), or -OC(O)(3- to 8-membered cycloalkylene)-Ci-ioalkylene;wherein each 6- to 10-membered arylene and 5- to 10-membered heteroarylene of Linker are independently optionally substituted with RLa,wherein each 4- to 12-membered heterocyclylene and 3- to 8- membered cycloalkylene of Linker are independently optionally substituted with RLb; andwherein each Ci-ioalkylene of Linker is independently optionally substituted with RLc;Ring D is optional, and when present is 4- to 12-membered heterocyclyl or 3- to 8-membered cycloalkyl, each of which is optionally substituted with one or more RD; andRing 4 is phenyl optionally substituted with one or more R4a, 5- to 10- membered heteroaryl optionally substituted with one or more R4a, 4- to 12-membered heterocyclyl optionally substituted with one or more R4b, or 3- to 8-membered cycloalkyl optionally substituted with one or more R4b;wherein Ring 4 and Ring 1 are connected via a bond, -N(Ry)-, -O-, - C(O)-, -C(0)N(Ry)-, -N(Ry)C(0)-, C(O)O-, -OC(O), or Ci-ioalkylene optionally substituted with one or more oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each Rla, R2a, R3a, and R4ais independently halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Cl.4alkylene-N(Rv)C(O)Cl.4alkyl, Ci- 4alkyleneC(O)N(Ry)-Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(0)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci-4alkyl, Ci- 4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(0)Ci-4alkyl of Rla, R2a, R3a, and R4ais optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rla, R2a, R3a, and R4ais optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rlb, R2b, R3b, and R4bis independently oxo, halo, OH, CN, C2alkynyl, Ci-4alkoxy, N(Ry)(Rz), N(Ry)C(O)Ci-4alkyl, C(O)N(Ry)Ci-4alkyl, Ci-4alkyl, Ci-4haloalkyl, Ci-4haloalkoxy, C(O)Ci-4alkyl, S(O)nRx, S(O)nN(Ry)(Rz), Ci-4alkylene-O-Ci-4alkyl, Ci-4alkylene-N(Ry)-Ci- 4alkyl, Ci-4alkylene-S(O)n-Ci-4alkyl, 3- to 8-membered cycloalkyl, or 4- to 12-membered heterocyclyl;wherein the C(O)Ci-4alkyl of Rlb, R2b, R3b, and R4bis optionally substituted with N(Ry)(Rz), and wherein the 4- to 12-membered heterocyclyl of Rlb, R2b, R3b, and R4bis optionally substituted with oxo, OH, or C(O)Ci-4alkyl;each Rx, Ry, and Rzis independently H, Ci-4alkyl, or Ci-4haloalkyl;n is 1 or 2;each RLais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl; andeach Rc, RD, RLb, and RLcis independently oxo, halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;each RCais independently halo, OH, Ci-4alkoxy, Ci-4alkyl, or Ci-4haloalkyl;wherein Q is Ring 3 or of formula (i) when R1is H, R2is H, and Ring 1 is 5-10 membered heteroaryl optionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

2. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are each F.

3. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are each H.

4. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together to form oxo.

5. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together along with the atoms to which they are attached to form 3- to 5-membered cycloalkyl.

6. The compound of claim 1 or 5, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together along with the atoms to which they are attached to form cyclopropyl.

7. The compound of any of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m is 0.

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

9. The compound of any of claims 1-8, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R3, R4, and R5are each H.

10. The compound of any of claims 1-8, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R3and R4are each Ci-4alkyl.

11. The compound of any of claims 1-8 or 10, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R5is H.

12. The compound of any of claims 1-11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rlaor 6- to 10-membered aryl optionally substituted with one or more Rla.

13. The compound of any of claims 1-12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is 5- to 10-membered heteroaryl optionally substituted with one or more Rla.

14. The compound of any of claims 1-12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is 6- to 10-membered aryl optionally substituted with one or more Rla.

15. The compound of any of claims 1-12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is:, each of which is optionally substituted with one or more Rla16. The compound of claim 15, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is:each of which is optionally substituted with one or more Rla.

17. The compound of claim 15 or 16, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is:, each of which is optionally substituted with one or more Rla.

18. The compound of any of claims 1-11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is 4- to 12-membered heterocyclyl optionally substituted with one or more Rlbor 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

19. The compound of any of claims 1-11 or 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is 4- to 12- membered heterocyclyl optionally substituted with one or more Rlb.

20. The compound of any of claims 1-11 or 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

21. The compound of claim 17, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 1 is:Q , which is optionally substituted with one or more Rla.

22. The compound of any of claims 1-21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 2 is phenyl optionally substituted with one or more R2a.

23. The compound of any of claims 1-22, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt of any of the foregoing, wherein Ring 2 isR2a.

24. The compound of any of claims 1-23, wherein Q is absent and the compound is of Formula (II):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing,wherein R2is F, R1and R2are taken together to form oxo, or R1and R2are taken together along with the atoms to which they are attached to form a 3- to 5-membered cycloalkyl or 3- to 5-membered heterocyclyl when Ring 1 is 5-10 membered heteroaryloptionally substituted with one or more Rla, 6-10 membered aryl optionally substituted with one or more Rla, or 3- to 8-membered cycloalkyl optionally substituted with one or more Rlb.

25. The compound of any of claims 1-23, wherein Q is Ring 3 and the compound is of Formula (III):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

26. The compound of any of claims 1-23 or 25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 3 is 6- to 10-membered aryl optionally substituted with one or more R3a.

27. The compound of any of claims 1-23, 25, or 26, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 3 is phenyl optionally substituted with one or more R3a.

28. The compound of any of claims 1-23 or 25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 3 is 4- to 12-membered heterocyclyl optionally substituted with one or more R3b.

29. The compound of any of claims 1-23, 25, or 28, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 3 is:H, each of which is optionally substituted with one or more R3b.

30. The compound of any of claims 1-23, wherein Q is of Formula (i) and the compound is of Formula (IV):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

31. The compound of any of claims 1 -23 or 30, or a stereoisomer or tautomer thereof, or a HOpharmaceutically acceptable salt of any of the foregoing, wherein Ring A isoptionally substituted with one or more groups independently selected from Ci-4alkyl and halo.

32. The compound of any of claims 1-23, 30, or 31, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X is a bond or -N(Ry)-.

33. The compound of any of claims 1-23 or 30-32, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X is a bond.

34. The compound of any of claims 1-23 or 30-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring B iswherein # indicates attachment to X.

35. The compound of any of claims 1-23 or 30-34, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein W is a bond or -CH2-.

36. The compound of any of claims 1-23 or 30-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring C is absent and W is a bond.

37. The compound of any of claims 1-23 or 30-35, or a stereoisomer or tautomer thereof,or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring C is, each of which is optionally substituted with one or more Rc.

38. The compound of any of claims 1-23 or 30-37, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Linker is Ci-loalkyleneC(O), C(0)Ci-ioalkylene, C(0)Ci-ioalkyleneC(0), -C(O)-, C(O)O-, -OC(O), -C(0)N(Ry)-, -N(Ry)C(0)-, -C(0)N(Ry)-Ci-ioalkylene, Ci-ioalkylene-C(0)N(Ry)-, -N(Ry)C(0)-Ci-ioalkylene, Ci-ioalkylene-N(Ry)C(0)-, C(O)O-(3- to 8-membered cycloalkylene)-Ci-ioalkylene, Ci-ioalkylene-OC(O).

39. The compound of any of claims 1-23 or 30-38, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring D is absent.

40. The compound of any of claims 1-23 or 30-39, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 4 is piperidinyl or cyclohexyl, each of which is optionally substituted with one or more R4b.

41. The compound of any of claims 1-23 or 30-40, or a stereoisomer or tautomer thereof,or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring 4 is, or , each of which is optionally substituted with one or more R4b.

42. The compound of any of claims 1-23, 30-36, 38, or 39-41, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring C and Ring D are each absent, W is a bond, and wherein Linker and Ring 4 are taken togetherO B B N, wherein p is 1-10, and wherein indicates the point of attachment to Ring 1.

43. The compound of any of claims 1-23, 30-35, or 37-41, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Ring D is absent, and wherein Ring C, Linker, and Ring 4 are taken together to formO o , wherein p is 1-10, and wherein indicates the point of attachment to Ring 1.

44. The compound of any of claims 1-43, wherein the compound is selected from the compounds provided in Table 1 and Table 2, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

45. The compound of claim 44, wherein the compound is selected from the compounds provided in Table 1, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

46. The compound of claim 44, wherein the compound is selected from the compounds provided in Table 2, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

47. A pharmaceutical composition, comprising a compound of any of claims 1-46, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient.

48. The pharmaceutical composition of claim 47, wherein the compound is a compound of any of claims 24-29 or 45, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient.

49. The pharmaceutical composition of claim 47, wherein the compound is a compound of any of claims 30-43 or 46, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient.

50. A method of inhibiting Pinl in a cell, comprising exposing the cell to a compound of any of claims 24-29 or 45, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 48.

51. A method of degrading Pinl in a cell, comprising exposing the cell to a compound of any of claims 30-43 or 46, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 49.

52. A method of treating a disease or disorder associated with Pinl, comprising administering to a subject in need thereof a compound of any of claims 1-46, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of any of claims 47-49.

53. The method of claim 52, wherein the disease or disorder is a cancer, fibrosis, hepatic injury, hepatic stress, hepatic inflammation, or fibroblast activation, or a combination thereof.

54. The method of claim 52 or 53, wherein the disease or disorder is a cancer.

55. The method of any of claims 52-54, wherein the cancer is brain cancer, bladder cancer, breast cancer, triple negative breast cancer, HER2-positive breast cancer, cervical cancer, colorectal cancer, colorectal carcinoma, colorectal carcinoma with microsatellite instability, colorectal carcinoma that is microsatellite stable, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, leukemia, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, Merkel cell carcinoma, multiple myeloma, pancreatic ductal carcinoma, or renal cell carcinoma.

56. The method of claim 55, wherein the cancer is brain cancer, breast cancer, triple negative breast cancer, HER2 -positive breast cancer, colorectal cancer, colorectal carcinoma, colorectal carcinoma with microsatellite instability, colorectal carcinoma that is microsatellite stable, or non-small cell lung cancer.

57. The method of claim 55 or 56, wherein the cancer is breast cancer.

58. The method of any of claims 55-57, wherein the breast cancer is triple negative breast cancer or HER2 -positive breast cancer.

59. The method of any of claims 55-58, wherein the breast cancer is triple negative breast cancer.

60. The method of claim 55 or 56, wherein the cancer is colorectal cancer.

61. The method of any of claims 55, 56, or 60, wherein the colorectal cancer is colorectal carcinoma, colorectal carcinoma with microsatellite instability, or colorectal carcinoma that is microsatellite stable.

62. The method of any of claims 55, 56, 60, or 61, wherein the colorectal cancer is associated with a hereditary syndrome.

63. The method of claim 55 or 56, wherein the cancer is non-small cell lung cancer.

64. The method of claim 52 or 53, wherein the disease or disorder is fibrosis.

65. The method of any of claims 52, 53, or 64, wherein the fibrosis is pulmonary fibrosis, idiopathic pulmonary fibrosis, scleroderma, myelofibrosis, kidney fibrosis, pancreas fibrosis, cardiac fibrosis, liver fibrosis, or MASH.

66. The method of claim 65, wherein the fibrosis is MASH, and the MASH is NASH or NAFLD.

67. The method of claim 52 or 53, wherein the disease or disorder is hepatic injury, hepatic stress, hepatic inflammation, or fibroblast activation.

68. The method of any of claims 52-67, wherein the subject is a human.

69. A compound of any of claims 1-46, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of any of claims 47-49, for use in treating a disease or disorder associated with Pinl in a subject in need thereof.

70. The compound for use of claim 69, wherein the disease or disorder is a cancer, fibrosis, hepatic injury, hepatic stress, hepatic inflammation, or fibroblast activation, or a combination thereof.

71. The compound for use of claim 69 or 70, wherein the disease or disorder is a cancer.

72. The compound for use of any of claims 69-71, wherein the cancer is brain cancer, bladder cancer, breast cancer, triple negative breast cancer, HER2 -positive breast cancer, cervical cancer, colorectal cancer, colorectal carcinoma, colorectal carcinoma with microsatellite instability, colorectal carcinoma that is microsatellite stable, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, leukemia, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, Merkel cell carcinoma, multiple myeloma, pancreatic ductal carcinoma, or renal cell carcinoma.

73. The compound for use of claim 72, wherein the cancer is brain cancer, breast cancer, triple negative breast cancer, HER2 -positive breast cancer, colorectal carcinoma, colorectalcarcinoma with microsatellite instability, colorectal carcinoma that is microsatellite stable, or non-small cell lung cancer.

74. The compound for use of claim 72 or 73, wherein the cancer is breast cancer, triple negative breast cancer, or HER2 -positive breast cancer.

75. The compound for use of any of claims 72-74, wherein the breast cancer is triple negative breast cancer or HER2-positive breast cancer.

76. The compound for use of any of claims 72-75, wherein the breast cancer is triple negative breast cancer.

77. The compound for use of claim 72 or 73, wherein the cancer is colorectal cancer.

78. The compound for use of any of claims 72, 73, or 77, wherein the colorectal cancer is colorectal carcinoma, colorectal carcinoma with microsatellite instability, or colorectal carcinoma that is microsatellite stable.

79. The compound for use of any of claims 72, 73, 77, or 78, wherein the colorectal cancer is associated with a hereditary syndrome.

80. The compound for use of claim 72 or 73, wherein the cancer is non-small cell lung cancer.

81. The compound for use of claim 69 or 70, wherein the disease or disorder is fibrosis.

82. The compound for use of any of claims 69, 70, or 71, wherein the fibrosis is pulmonary fibrosis, idiopathic pulmonary fibrosis, scleroderma, myelofibrosis, kidney fibrosis, pancreas fibrosis, cardiac fibrosis, liver fibrosis, or MASH.

83. The compound for use of claim 82, wherein the fibrosis is MASH, and the MASH is NASH orNAFLD.

84. The compound for use of claim 69 or 70, wherein the disease or disorder is hepatic injury, hepatic stress, hepatic inflammation, or fibroblast activation.

85. The compound for use of any of claims 69-84, wherein the subject is a human.

86. Use of a compound of any of claims 1-46, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition ofany of claims 47-49, for the manufacture of a medicament for treating a disease or disorder associated with Pinl in a subject in need thereof.

87. The use of claim 86, wherein the disease or disorder is a cancer, fibrosis, hepatic injury, hepatic stress, hepatic inflammation, or fibroblast activation, or a combination thereof.

88. The use of claim 86 or 87, wherein the disease or disorder is a cancer.

89. The use of any of claims 86-88, wherein the cancer is brain cancer, bladder cancer, breast cancer, triple negative breast cancer, HER2-positive breast cancer, cervical cancer, colorectal cancer, colorectal carcinoma, colorectal carcinoma with microsatellite instability, colorectal carcinoma that is microsatellite stable, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, leukemia, lung cancer, small cell lung cancer, nonsmall cell lung cancer, lymphoma, melanoma, Merkel cell carcinoma, multiple myeloma, pancreatic ductal carcinoma, or renal cell carcinoma.

90. The use of claim 89, wherein the cancer is brain cancer, breast cancer, triple negative breast cancer, HER2-positive breast cancer, colorectal carcinoma, colorectal carcinoma with microsatellite instability, colorectal carcinoma that is microsatellite stable, or non-small cell lung cancer.

91. The use of claim 89 or 90, wherein the cancer is breast cancer, triple negative breast cancer, or HER2-positive breast cancer.

92. The use of any of claims 89-91, wherein the breast cancer is triple negative breast cancer or HER2 -positive breast cancer.

93. The use of any of claims 89-92, wherein the breast cancer is triple negative breast cancer.

94. The use of claim 89 or 90, wherein the cancer is colorectal cancer.

95. The use of any of claims 89, 90, or 94, wherein the colorectal cancer is colorectal carcinoma, colorectal carcinoma with microsatellite instability, or colorectal carcinoma that is microsatellite stable.

96. The use of any of claims 89, 90, 94, or 95, wherein the colorectal cancer is associated with a hereditary syndrome.

97. The use of claim 89 or 90, wherein the cancer is non-small cell lung cancer.

98. The use of claim 86 or 87, wherein the disease or disorder is fibrosis.

99. The use of any of claims 86, 87, or 98, wherein the fibrosis is pulmonary fibrosis, idiopathic pulmonary fibrosis, scleroderma, myelofibrosis, kidney fibrosis, pancreas fibrosis, cardiac fibrosis, liver fibrosis, or MASH.

100. The use of claim 99, wherein the fibrosis is MASH, and the MASH is NASH or NAFLD.

101. The use of claim 86 or 87, wherein the disease or disorder is hepatic injury, hepatic stress, hepatic inflammation, or fibroblast activation.

102. The use of any of claims 86-101, wherein the subject is a human.

103. A kit comprising: (i) a compound of any of claims 1-46, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of any of claims 47-49, and (ii) instructions for use in treating a disease or disorder associated with Pinl in a subject in need thereof.

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