WO2021231778A1

WO2021231778A1 - Coronavirus protease degraders and uses thereof

Info

Publication number: WO2021231778A1
Application number: PCT/US2021/032318
Authority: WO
Inventors: Christopher M. Yates; Xiaozhang Zheng; Xiao Zhu
Original assignee: Kymera Therapeutics, Inc.
Priority date: 2020-05-13
Filing date: 2021-05-13
Publication date: 2021-11-18

Abstract

The present invention provides compounds, compositions thereof, and methods of using the same.

Description

CORONAVIRUS PROTEASE DEGRADERS AND USES THEREOF REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Appl. No. 63/024,115, filed May 13, 2020 and U.S. Provisional Appl. No.63/123,123, filed December 9, 2020, the contents of which are herein incorporated by reference. TECHNICAL FIELD OF THE INVENTION [0002] The present invention relates to compounds and methods useful for the modulation of coronavirus protease via ubiquitination and/or degradation by compounds according to the present invention. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. BACKGROUND OF THE INVENTION [0003] Ubiquitin-Proteasome Pathway (UPP) is a critical pathway that regulates key regulator proteins and degrades misfolded or abnormal proteins. UPP is central to multiple cellular processes, and if defective or imbalanced, it leads to pathogenesis of a variety of diseases. The covalent attachment of ubiquitin to specific protein substrates is achieved through the action of E3 ubiquitin ligases. [0004] There are over 600 E3 ubiquitin ligases which facilitate the ubiquitination of different proteins in vivo, which can be divided into four families: HECT-domain E3s, U-box E3s, monomeric RING E3s and multi-subunit E3s. See generally Li et al. (PLOS One, 2008, 3, 1487) titled “Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling.”; Berndsen et al. (Nat. Struct. Mol. Biol., 2014, 21, 301-307) titled “New insights into ubiquitin E3 ligase mechanism”; Deshaies et al. (Ann. Rev. Biochem., 2009, 78, 399- 434) titled “RING domain E3 ubiquitin ligases.”; Spratt et al. (Biochem.2014, 458, 421-437) titled “RBR E3 ubiquitin ligases: new structures, new insights, new questions.”; and Wang et al. (Nat. Rev. Cancer., 2014, 14, 233-347) titled “Roles of F-box proteins in cancer.” [0005] UPP plays a key role in the degradation of short-lived and regulatory proteins important in a variety of basic cellular processes, including regulation of the cell cycle, modulation of cell surface receptors and ion channels, and antigen presentation. The pathway has been implicated in several forms of malignancy, in the pathogenesis of several genetic diseases (including cystic fibrosis, Angelman’s syndrome, and Liddle syndrome), in immune surveillance/viral pathogenesis, and in the pathology of muscle wasting. Many diseases are associated with an abnormal UPP and negatively affect cell cycle and division, the cellular response to stress and to extracellular modulators, morphogenesis of neuronal networks, modulation of cell surface receptors, ion channels, the secretory pathway, DNA repair and biogenesis of organelles. [0006] Aberrations in the process have recently been implicated in the pathogenesis of several diseases, both inherited and acquired. These diseases fall into two major groups: (a) those that result from loss of function with the resultant stabilization of certain proteins, and (b) those that result from gain of function, i.e. abnormal or accelerated degradation of the protein target. [0007] The UPP is used to induce selective protein degradation, including use of fusion proteins to artificially ubiquitinate target proteins and synthetic small-molecule probes to induce proteasome- dependent degradation. Bifunctional compounds composed of a target protein-binding ligand and an E3 ubiquitin ligase ligand, induced proteasome-mediated degradation of selected proteins via their recruitment to E3 ubiquitin ligase and subsequent ubiquitination. These drug-like molecules offer the possibility of temporal control over protein expression. Such compounds are capable of inducing the inactivation of a protein of interest upon addition to cells or administration to an animal or human, and could be useful as biochemical reagents and lead to a new paradigm for the treatment of diseases by removing pathogenic or oncogenic proteins (Crews C, Chemistry & Biology, 2010, 17(6):551-555; Schnnekloth JS Jr., Chembiochem, 2005, 6(l):40-46). [0008] Coronaviruses, originally discovered in the 1960s, are enveloped, positive-sense, single- stranded RNA viruses that target cells via the viral structural spike (S) protein that binds to a host receptor and then fuses with the host membrane. Upon cell entry, viral RNA attaches to host ribosomes in order to produce two polyproteins which are essential for viral replication. The proteolytic cleavage of these two polyproteins is carried out by 3C-like protease (3CLpro) and the papain-like protease (PLpro). See e.g., Ghosh et al., ChemMedChem 2020, doi: 10.1002/cmdc.202000223. [0009] Coronaviruses are prevalent in both humans and wildlife, causing both intestinal and respiratory infections. To date, there are seven known human pathogenic coronaviruses that cause infections with varying degrees of severity. Four common strains cause only mild respiratory infections, primarily in immunocompromised individuals, and include the alphacoronaviruses HCoV-NL63 and HCoV-229E, and the betacoronaviruses HCoV-OC43 and HKU1 (Cui et al., Nat. Rev. Microbiol.2019, 17:181-92). However, in the past two decades alone, at least three zoonotic strains causing more severe and lethal infections have emerged around the world. These betacoronoviruses cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently COVID-19 disease, and the associated pathogens are named SARS-CoV, MERS-CoV, and SARS-CoV-2, respectively. Taken together, SARS, MERS, and COVID-19 have caused severe respiratory infections and resulted in high fatality rates (S1, S2) throughout the population. [0010] SARS-CoV-2 is a previously unidentified strain of coronavirus that has 82% sequence identity to SARS-CoV and causes the novel coronavirus-based disease COVID-19. The COVID-19 pandemic has had a crippling effect on the global economy and stressed the health care infrastructure. There is an urgent need for treatments of COVID-19 and broad-spectrum antivirals for the treatment of both known and novel coronaviruses. An attractive target for drug discovery is 3CLpro, an enzyme of 305 amino acid residues that is critical to the SARS-CoV-2 viral life cycle (Zhang et al., Science 2020, 10.1126/science.abb3405). This cysteine protease is one of the most highly conserved targets in the coronavirus family, also making it an attractive target for the development of broad spectrum antivirals against the coronavirus family including undetected and future strains (Wang, F., Chen, C., Tan, W. et al. Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design. Sci Rep 6, 22677 (2016); Qamar et al., J. Pharm. Anal., doi.org/10.1016/j.jpha.2020.03.009 (2020); Pillaiyar et al., J. Med. Chem.2016, 59, 14, 6595-6628). Since the specific cleavage sites for SARS-CoV-23CLpro are not found in any human proteases, therapeutics directed at this target are not likely to be toxic (Zhang et al., J. Med. Chem.2020, doi.org/10.1021/acs.jmedchem.9b01828). [0011] One of the key challenges to targeting viral cysteine proteases, like SARS-CoV-23CLpro, is the need to have extremely potent inhibitors with prolonged catalytic site occupancy. This is typically achieved using electrophilic warheads that take advantage of the catalytic cysteine to form covalent complexes. In certain embodiments, bifunctional molecules will contain covalent, or reversible covalent 3CLpro binders that take advantage of strong binding to drive efficient, complete degradation of the target enzyme. In separate embodiments, bifunctional molecules will contain noncovalent 3CLpro binders offer an opportunity to take advantage of the catalytic nature of the degrader technology. Since there are currently no established vaccines or effective antiviral drugs directed against the pathogens SARS-CoV, SARS-CoV- 2, or MERS-CoV, the unmet need for new therapeutics remains stronger than ever. SUMMARY OF THE INVENTION [0012] The present application relates novel bifunctional compounds, which function to recruit coronavirus protease protein to E3 ubiquitin ligase for degradation, and methods of preparation and uses thereof. In particular, the present disclosure provides bifunctional compounds, which find utility as modulators of targeted ubiquitination of coronavirus protease, which is then degraded and/or otherwise inhibited by the bifunctional compounds as described herein. Also provided are monovalent compounds, which find utility as inducers of targeted ubiquitination of coronavirus protease, which are then degraded and/or otherwise inhibited by the monovalent compounds as described herein. An advantage of the compounds provided herein is that a broad range of pharmacological activities is possible, consistent with the degradation/inhibition of coronavirus protease. In addition, the description provides methods of using an effective amount of the compounds as described herein for the treatment or amelioration of a disease condition, such those caused by coronavirus infection. [0013] The present application further relates to targeted degradation of coronavirus protease protein through the use of bifunctional molecules, including bifunctional molecules that link a cereblon-binding moiety to a ligand that binds coronavirus protease protein. [0014] It has now been found that compounds of this invention, and pharmaceutically acceptable compositions thereof, are effective as degraders of coronavirus protease. Such compounds have the general formula I:

or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein. [0015] Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful for treating a variety of diseases, disorders or conditions, associated with regulation of coronavirus protease protein. Such diseases, disorders, or conditions include those described herein. [0016] Compounds provided by this invention are also useful for the study of coronavirus protease protein in biological and pathological phenomena; and the comparative evaluation of new coronavirus protease inhibitors or coronavirus protease degraders, in vitro or in vivo. BRIEF DESCRIPTION OF THE DRAWINGS [0017] FIGS.1A-1B show the 3CLpro sequence of SARS-CoV-2, and ORF1a mutations present in the NCBI SARS-CoV-2 sequence database (taxid: 2697049; up to April 26, 2020). FIG.1A shows the canonical 3CLpro sequence (SEQ ID NO:1). Observed amino acid mutations are shown below their specific sites in SEQ ID NO:1 (bolded). FIG.1B shows 3CLpro mutation frequencies and associated accession numbers for the ORF1a sequences in the NCBI SARS-CoV-2 database. DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 1. General Description of Certain Embodiments of the Invention: [0018] Compounds of the present invention, and compositions thereof, are useful as degraders and/or inhibitors of coronavirus protease protein. In some embodiments, a provided compound degrades and/or inhibits coronavirus protease protein. [0019] In certain embodiments, the present invention provides a compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein: PBM is a protease binding moiety capable of binding coronavirus protease; L is a bivalent moiety that connects PBM to DIM; and DIM is a degradation inducing moiety, such as a ligase binding moiety (LBM), lysine mimetic, or hydrogen atom. 2. Compounds and Definitions: [0020] Compounds of the present invention include those described generally herein, and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry”, 5^th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference. [0021] The term “aliphatic” or “aliphatic group”, as used herein, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic, bicyclic, bridged bicyclic, or spirocyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as "carbocycle," “cycloaliphatic” or “cycloalkyl”), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms. In some embodiments, “cycloaliphatic” (or “carbocycle” or “cycloalkyl”) refers to a monocyclic C3-C6 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. [0022] As used herein, the term “bridged bicyclic” refers to any bicyclic ring system, i.e. carbocyclic or heterocyclic, saturated or partially unsaturated, having at least one bridge. As defined by IUPAC, a “bridge” is an unbranched chain of atoms or an atom or a valence bond connecting two bridgeheads, where a “bridgehead” is any skeletal atom of the ring system which is bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, a bridged bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include those groups set forth below where each group is attached to the rest of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise specified, a bridged bicyclic group is optionally substituted with one or more substituents as set forth for aliphatic groups. Additionally or alternatively, any substitutable nitrogen of a bridged bicyclic group is optionally substituted. Exemplary bridged bicyclics include:

[0023] The term “lower alkyl” refers to a C_1-4 straight or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl. [0024] The term “lower haloalkyl” refers to a C_1-4 straight or branched alkyl group that is substituted with one or more halogen atoms. [0025] The term “heteroatom” means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quaternized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR⁺ (as in N-substituted pyrrolidinyl)). [0026] The term "unsaturated," as used herein, means that a moiety has one or more units of unsaturation. [0027] As used herein, the term “bivalent C_1-8 (or C_1-6) saturated or unsaturated, straight or branched, hydrocarbon chain”, refers to bivalent alkylene, alkenylene, and alkynylene chains that are straight or branched as defined herein. [0028] The term “alkylene” refers to a bivalent alkyl group. An “alkylene chain” is a polymethylene group, i.e., –(CH₂)_n–, wherein n is a positive integer, preferably from 1 to 6, from 1 to 4, from 1 to 3, from 1 to 2, or from 2 to 3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group. [0029] The term “alkenylene” refers to a bivalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group. [0030] As used herein, the term “cyclopropylenyl” refers to a bivalent cyclopropyl group of the following structure:

. [0031] The term “halogen” means F, Cl, Br, or I. [0032] The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic or bicyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. The term “aryl” may be used interchangeably with the term “aryl ring.” In certain embodiments of the present invention, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non–aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like. [0033] The terms “heteroaryl” and “heteroar–,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 ^ electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar–”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H–quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3–b]–1,4–oxazin–3(4H)–one. A heteroaryl group may be mono– or bicyclic. A heteroaryl ring may include one or more oxo (=O) or thioxo (=S) substituent. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. [0034] As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5– to 7–membered monocyclic or 7–10– membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term "nitrogen" includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0–3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4–dihydro–2H–pyrrolyl), NH (as in pyrrolidinyl), or ⁺NR (as in N–substituted pyrrolidinyl). [0035] A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H–indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. A heterocyclyl group may be monocyclic, bicyclic, bridged bicyclic, or spirocyclic. A heterocyclic ring may include one or more oxo (=O) or thioxo (=S) substituent. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted. [0036] As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined. [0037] As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted” means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein. [0038] Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; –(CH₂)_0–4R°; –(CH₂)_0–4OR°; -O(CH₂)_0-4R°, –O–(CH₂)_0–4C(O)OR°; – (CH₂)_0–4CH(OR°)₂; –(CH₂)_0–4SR°; –(CH₂)_0–4Ph, which may be substituted with R°; –(CH₂)_0–4O(CH₂)_0–1Ph which may be substituted with R°; –CH=CHPh, which may be substituted with R°; –(CH₂)_0–4O(CH₂)_0–1- pyridyl which may be substituted with R°; –NO₂; –CN; –N3; -(CH₂)_0–4N(R°)₂; –(CH₂)_0–4N(R°)C(O)R°; – N(R°)C(S)R°; –(CH₂)_0–4N(R°)C(O)NR°₂; -N(R°)C(S)NR°₂; –(CH₂)_0–4N(R°)C(O)OR°; – N(R°)N(R°)C(O)R°; -N(R°)N(R°)C(O)NR°₂; -N(R°)N(R°)C(O)OR°; –(CH₂)_0–4C(O)R°; –C(S)R°; – (CH₂)_0–4C(O)OR°; –(CH₂)_0–4C(O)SR°; -(CH₂)_0–4C(O)OSiR°₃; –(CH₂)_0–4OC(O)R°; –OC(O)(CH₂)_0–4SR°; – (CH₂)_0–4SC(O)R°; –(CH₂)_0–4C(O)NR°₂; –C(S)NR°₂; –C(S)SR°; –SC(S)SR°, -(CH₂)0– 4OC(O)NR°₂; -C(O)N(OR°)R°; –C(O)C(O)R°; –C(O)CH₂C(O)R°; –C(NOR°)R°; -(CH₂)_0–4SSR°; –(CH₂)_0– ₄S(O)₂R°; –(CH₂)_0–4S(O)₂OR°; –(CH₂)_0–4OS(O)₂R°; –S(O)₂NR°₂; -(CH₂)_0–4S(O)R°; -N(R°)S(O)₂NR°₂; – N(R°)S(O)₂R°; –N(OR°)R°; –C(NH)NR°₂; –P(O)₂R°; -P(O)R°₂; -OP(O)R°₂; –OP(O)(OR°)₂; SiR°₃; –(C_1–4 straight or branched alkylene)O–N(R°)₂; or –(C1–4 straight or branched alkylene)C(O)O–N(R°)₂, wherein each R° may be substituted as defined below and is independently hydrogen, C1–6 aliphatic, –CH₂Ph, – O(CH₂)_0–1Ph, -CH₂-(5-6 membered heteroaryl ring), or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R°, taken together with their intervening atom(s), form a 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below. [0039] Suitable monovalent substituents on R° (or the ring formed by taking two independent occurrences of R° together with their intervening atoms), are independently halogen, -(CH2)o-2R^●, - (haloR^●), -(CH₂)O-₂OH, -(CH₂)O-20R^●, -(CH₂)O-2CH(OR^●)₂; -0(haloR^●), -CN, -N₃, -(CH₂)o-₂C(O)R^●, - (CH₂)O-2C(O)OH, -(CH₂)O-2C(0)OR^●, -(CH₂)O-2SR^●, -(CH₂)O-₂SH, -(CH₂)O-2NH₂, -(CH₂)O-2NHR·, - (CH2)_O-2NR^●2, -NO₂, -SiR^●3, -OSiR^●3, -C(O)SR* — (C 1-4 straight or branched alkylene)C(O)OR^●, or - SSR^● wherein each R* is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C_1-4 aliphatic, -CH₂Ph, -0(CH₂)_0–1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R° include =0 and =S. [0040] Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =0, =S, =NNR^*2, =NNHC(O)R^*, =NNHC(O)OR\ =NNHS(O)₂R^*, =NR^* =NOR^*, - 0(C(R^*2))2-30-, or-S(C(R^*2))2-3S-, wherein each independent occurrence of R^* is selected from hydrogen, C_1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: -0(CR^*2)_2-3O-, wherein each independent occurrence of R^* is selected from hydrogen, C_1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0041] Suitable substituents on the aliphatic group of R^* include halogen, -R^●, -(haloR^●), -OH, -OR^●, -0(haloR^●), -CN, -C(O)OH, -C(O)OR^●, -NH₂, -NHR^●, -NR^● ₂, or -NO₂, wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1-4 aliphatic, -CH₂Ph, -O(CH₂)_0–1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0042] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include - R^†, -NR^†2, -C(O)R^†, -C(O)OR^†, -C(O)C(O)R^†, -C(O)CH₂C(O)R^†, -S(O)₂R^†, -S(O)₂NR^† ₂, -C(S)NR^†2, - C(NH)NR^†2, or -N(R^†)S(0)2R^†; wherein each R^† is independently hydrogen, C_1-6 aliphatic which may be substituted as defined below, unsubstituted -OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R^†, taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0043] Suitable substituents on the aliphatic group of R^† are independently halogen, -R^●, -(haloR^●), - OH, -OR^●, -0(haloR^●), -CN, -C(O)OH, -C(O)OR^●, -NH₂, -NHR^●, -NR^● ₂, or -N0₂, wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C_1–4 aliphatic, –CH₂Ph, –O(CH₂)_0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [0044] As used herein, a warhead group, e.g.,

, is capable of covalently binding, non- covalently binding, or reversibly binding to an amino acid residue (such as cysteine, lysine, histidine, or other residues capable of being covalently, non-covalently, or reversibly modified) present in the binding pocket of a target protein, for example, a coronavirus protease, thereby reversibly or irreversibly modulating the protein. [0045] In some embodiments, a warhead group is capable of covalently binding to cysteine. In some embodiments, a warhead group is capable of covalently binding to serine. In some embodiments, a warhead group is capable of covalently binding to lysine. In some embodiments, a warhead group is capable of covalently binding to a coronavirus protease. In certain aspects, the binding is covalent and results in targeted ubiquitination of coronavirus protease. [0046] In some embodiments, a warhead group is capable of non-covalently binding to cysteine. In some embodiments, a warhead group is capable of non-covalently binding to serine. In some embodiments, a warhead group is capable of non-covalently binding to lysine. In some embodiments, a warhead group is capable of non-covalently binding to a coronavirus protease. In certain aspects, the binding is non-covalent and results in targeted ubiquitination of coronavirus protease. [0047] In some embodiments, a warhead group is capable of reversibly binding to cysteine. In some embodiments, a warhead group is capable of reversibly binding to serine. In some embodiments, a warhead group is capable of reversibly binding to lysine. In some embodiments, a warhead group is capable of reversibly binding to a coronavirus protease. In certain aspects, the binding is covalent and results in targeted ubiquitination of coronavirus protease. [0048] As used herein, the term "pharmaceutically acceptable salt" refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1–19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2–naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p–toluenesulfonate, undecanoate, valerate salts, and the like. [0049] Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N⁺(C1–4alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate. In some embodiments, the provided compounds are purified in salt form for convenience and/or ease of purification, e.g., using an acidic or basic mobile phase during chromatography. Salts forms of the provided compounds formed during chromotagraphic purification are contemplated herein and are readily apparent to those having skill in the art. [0050] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a ¹³C- or ¹⁴C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention [0051] As used herein, the term “provided compound” refers to any genus, subgenus, and/or species set forth herein. [0052] As used herein, the term “inhibitor” is defined as a compound that binds to and /or inhibits coronavirus protease with measurable affinity. In certain embodiments, an inhibitor has an IC₅₀ and/or binding constant of less than about 50 ^M, less than about 1 ^M, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM. [0053] As used herein, the term “degrader” is defined as a heterobifunctional compound that binds to and/or inhibits both coronavirus protease and an E3 ligase with measurable affinity resulting in the ubiquitination and subsequent degradation of the coronavirus protease. In certain embodiments, a degrader has an DC₅₀ of less than about 50 ^M, less than about 1 ^M, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM. As used herein, the term “monovalent” refers to a degrader compound without an appended E3 ligase binding moiety. [0054] A compound of the present invention may be tethered to a detectable moiety. It will be appreciated that such compounds are useful as imaging agents. One of ordinary skill in the art will recognize that a detectable moiety may be attached to a provided compound via a suitable substituent. As used herein, the term “suitable substituent” refers to a moiety that is capable of covalent attachment to a detectable moiety. Such moieties are well known to one of ordinary skill in the art and include groups containing, e.g., a carboxylate moiety, an amino moiety, a thiol moiety, or a hydroxyl moiety, to name but a few. It will be appreciated that such moieties may be directly attached to a provided compound or via a tethering group, such as a bivalent saturated or unsaturated hydrocarbon chain. In some embodiments, such moieties may be attached via click chemistry. In some embodiments, such moieties may be attached via a 1,3-cycloaddition of an azide with an alkyne, optionally in the presence of a copper catalyst. Methods of using click chemistry are known in the art and include those described by Rostovtsev et al., Angew. Chem. Int. Ed.2002, 41:2596-9 and Sun et al., Bioconjugate Chem., 2006, 17:52-7. [0055] As used herein, the term “detectable moiety” is used interchangeably with the term "label" and relates to any moiety capable of being detected, e.g., primary labels and secondary labels. Primary labels, such as radioisotopes (e.g., tritium, ³²P, ³³P, ³⁵S, or ¹⁴C), mass-tags, and fluorescent labels are signal generating reporter groups which can be detected without further modifications. Detectable moieties also include luminescent and phosphorescent groups. [0056] The term “secondary label” as used herein refers to moieties such as biotin and various protein antigens that require the presence of a second intermediate for production of a detectable signal. For biotin, the secondary intermediate may include streptavidin-enzyme conjugates. For antigen labels, secondary intermediates may include antibody-enzyme conjugates. Some fluorescent groups act as secondary labels because they transfer energy to another group in the process of nonradiative fluorescent resonance energy transfer (FRET), and the second group produces the detected signal. [0057] The terms “fluorescent label”, “fluorescent dye”, and “fluorophore” as used herein refer to moieties that absorb light energy at a defined excitation wavelength and emit light energy at a different wavelength. Examples of fluorescent labels include, but are not limited to: Alexa Fluor dyes (Alexa Fluor 350, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660 and Alexa Fluor 680), AMCA, AMCA-S, BODIPY dyes (BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY TR, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591, BODIPY 630/650, BODIPY 650/665), Carboxyrhodamine 6G, carboxy-X- rhodamine (ROX), Cascade Blue, Cascade Yellow, Coumarin 343, Cyanine dyes (Cy3, Cy5, Cy3.5, Cy5.5), Dansyl, Dapoxyl, Dialkylaminocoumarin, 4',5'-Dichloro-2',7'-dimethoxy-fluorescein, DM-NERF, Eosin, Erythrosin, Fluorescein, FAM, Hydroxycoumarin, IRDyes (IRD40, IRD 700, IRD 800), JOE, Lissamine rhodamine B, Marina Blue, Methoxycoumarin, Naphthofluorescein, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, PyMPO, Pyrene, Rhodamine B, Rhodamine 6G, Rhodamine Green, Rhodamine Red, Rhodol Green, 2',4',5',7'-Tetra-bromosulfone-fluorescein, Tetramethyl-rhodamine (TMR), Carboxytetramethylrhodamine (TAMRA), Texas Red, Texas Red-X. [0058] The term “mass-tag” as used herein refers to any moiety that is capable of being uniquely detected by virtue of its mass using mass spectrometry (MS) detection techniques. Examples of mass-tags include electrophore release tags such as N-[3-[4’-[(p-Methoxytetrafluorobenzyl)oxy]phenyl]-3- methylglyceronyl]isonipecotic Acid, 4’-[2,3,5,6-Tetrafluoro-4-(pentafluorophenoxyl)]methyl acetophenone, and their derivatives. The synthesis and utility of these mass-tags is described in United States Patents 4,650,750, 4,709,016, 5,360,8191, 5,516,931, 5,602,273, 5,604,104, 5,610,020, and 5,650,270. Other examples of mass-tags include, but are not limited to, nucleotides, dideoxynucleotides, oligonucleotides of varying length and base composition, oligopeptides, oligosaccharides, and other synthetic polymers of varying length and monomer composition. A large variety of organic molecules, both neutral and charged (biomolecules or synthetic compounds) of an appropriate mass range (100-2000 Daltons) may also be used as mass-tags. [0059] The terms “measurable affinity” and “measurably inhibit,” as used herein, means a measurable change in coronavirus protease activity between a sample comprising a compound of the present invention, or composition thereof, and coronavirus protease, and an equivalent sample comprising coronavirus protease, in the absence of said compound, or composition thereof. 3. Description of Exemplary Embodiments: [0060] As described above, in certain embodiments, the present invention provides a compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein: PBM is a protease binding moiety capable of binding coronavirus protease; L is a bivalent moiety that connects PBM to DIM; and DIM is a degradation inducing moiety, such as a ligase binding moiety (LBM), lysine mimetic, or hydrogen atom. Protease Binding Moiety (PBM) [0061] As defined herein and described above, PBM is a protease binding moiety capable of binding coronavirus protease. In some embodiments, PBM binds to coronavirus protease which then undergoes ubiquitination thereby marking the coronavirus protease for degradation via the Ubiquitin-Proteasome Pathway (UPP). In some embodiments, the coronavirus protease is a cysteine protease. In some embodiments, PBM binds covalently to coronavirus protease. In some embodiments, PBM binds non- covalently to coronavirus protease. In some embodiments, the binding of PBM to coronavirus protease is reversible. [0062] As defined herein and described below, wherein a formula is depicted using square brackets, e.g.,

, L is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom within PBM including substitution or replacement of a defined group in PBM. [0063] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaa-1:

aaa or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described herein, and wherein: R^v is R^A, -NR₂, -NRCOR, or

each R^A is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur. y is 0, 1, or 2; R^w is R^A,

z is 0, 1, 2, 3, or 4; Ring X is a ring selected from phenyl, a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, - Si(R)3, -S(O)₂R, -S(O)₂N(R)₂, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R2, -OP(O)(OR)₂, - OP(O)(OR)(NR2), -OP(O)(NR2)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R2, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR2), -N(R)P(O)(NR2)₂, or -N(R)S(O)₂R; R^x is hydrogen or R^A; and R^y is hydrogen, -OR, or R^A. [0064] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaa-2:

or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described herein, and wherein: R^v is R^A, -NR2, -NRCOR, or

z is 0, 1, 2, 3, or 4; Ring X is a ring selected from phenyl, a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or -N(R)S(O)₂R; and R^x is hydrogen or R^A. [0065] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaa-3:

I-aaa-3 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described herein, and wherein:

each R^A is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur.

z is 0, 1, 2, 3, or 4; Ring X is a ring selected from phenyl, a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or -N(R)S(O)₂R; R^x is hydrogen or R^A; and R^y is hydrogen, -OR, or R^A. [0066] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaa-4:

I-aaa-4 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described herein, and wherein:

z is 0, 1, 2, 3, or 4; Ring X is a ring selected from phenyl, a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R2, -OP(O)(OR)₂, - OP(O)(OR)(NR2), -OP(O)(NR2)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R2, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR2), -N(R)P(O)(NR2)₂, or -N(R)S(O)₂R; R^x is hydrogen or R^A; and R^y is hydrogen, -OR, or R^A. [0067] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaa-5:

I-aaa-5 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described herein, and wherein: R^v is R^A, -NR2, -NRCOR, or

z is 0, 1, 2, 3, or 4; Ring X is a ring selected from phenyl, a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or -N(R)S(O)₂R; R^x is hydrogen or R^A; and

warhead group. [0068] As defined about and described herein, R^v is R^A, -NR₂, -NRCOR, or

. [0069] In some embodiments, R^v is R^A. In some embodiments, R^v is -NR₂. In some embodiments, R^v is -NRCOR. In some embodiments, R^v is

. In some embodiments, R^v is -NMeCOMe. In some embodiments, R^v is In some embodiments, R^v is In some embodiments, R^v is

[0070] In certain embodiments, R^v is as depicted in the compounds of Table 2. [0071] As defined about and described herein, y is 0, 1, or 2. [0072] In some embodiments, y is 0. In some embodiments, y is 1. In some embodiments, y is 2. [0073] In certain embodiments, y is as depicted in the compounds of Table 2. [0074] about and described herein, R^w

As defined is R^A, ,

[0075] In some embodiments, R^w is R^A. In some embodiments,

. In some embodiments,

some embodiments, R^w is

. [0076] In some embodiments, R^w is

In some embodiments, R^w is

[0077] In certain embodiments, R^w is as depicted in the compounds of Table 2. _[0078] As defined about and described herein, each R^A is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [0079] In some embodiments, R^A is an optionally substituted C_1-6 aliphatic. In some embodiments, R^A is an optionally substituted phenyl. In some embodiments, R^A is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R^A is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [0080] In certain embodiments, R^A is as depicted in the compounds of Table 2. [0081] As defined about and described herein, Ring X is a ring selected from phenyl, a 5 to 7- membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. [0082] In some embodiments, Ring X is phenyl. In some embodiments, Ring X is a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Ring X is a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. [0083] In some embodiments, Ring X is

In some embodiments, Ring X is

. [0084] In certain embodiments, Ring X is as depicted in the compounds of Table 2. _[0085] As defined about and described herein, each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, -Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)N(R)₂, -C(O)N(R)OR, -C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, - OP(O)R₂, -OP(O)(OR)₂, -OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, - N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or -N(R)S(O)₂R; [0086] In some embodiments, R^z is hydrogen. In some embodiments, R^z is R^A. In some embodiments, R^z is halogen. In some embodiments, R^z is -CN. In some embodiments, R^z is -NO₂. In some embodiments, R^z is -OR. In some embodiments, R^z is -SR, -N(R)₂. In some embodiments, R^z is -Si(R)₃. In some embodiments, R^z is -S(O)₂R. In some embodiments, R^z is -S(O)₂N(R)₂. In some embodiments, R^z is -S(O)R. In some embodiments, R^z is -C(O)R. In some embodiments, R^z is -C(O)OR. In some embodiments, R^z is -C(O)N(R)₂. In some embodiments, R^z is -C(O)N(R)OR. In some embodiments, R^z is -C(R)₂N(R)C(O)R. In some embodiments, R^z is -C(R)₂N(R)C(O)N(R)₂. In some embodiments, R^z is -OC(O)R. In some embodiments, R^z is -OC(O)N(R)₂. In some embodiments, R^z is -OP(O)R₂. In some embodiments, R^z is -OP(O)(OR)₂. In some embodiments, R^z is -OP(O)(OR)(NR₂) . In some embodiments, R^z is -OP(O)(NR2)₂-. In some embodiments, R^z is -N(R)C(O)OR. In some embodiments, R^z is -N(R)C(O)R. In some embodiments, R^z is -N(R)C(O)N(R)₂. In some embodiments, R^z is -N(R)S(O)₂R. In some embodiments, R^z is -NP(O)R2. In some embodiments, R^z is -N(R)P(O)(OR)₂. In some embodiments, R^z is -N(R)P(O)(OR)(NR₂) . In some embodiments, R^z is -N(R)P(O)(NR₂)₂. In some embodiments, R^z is -N(R)S(O)₂R. [0087] In certain embodiments, R^z is as depicted in the compounds of Table 2. [0088] As defined about and described herein, each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur. [0089] In some embodiments, R is hydrogen. In some embodiments, R is an optionally substituted C1- 6 aliphatic. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, two R groups on the same nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur. [0090] In certain embodiments, R is as depicted in the compounds of Table 2. [0091] As defined about and described herein, z is 0, 1, 2, 3, or 4. [0092] In some embodiments, z is 0. In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is 4. [0093] In certain embodiments, z is as depicted in the compounds of Table 2. [0094] As defined about and described herein, R^x is hydrogen or R^A. [0095] In some embodiments, R^x is hydrogen. In some embodiments, R^x is R^A. _[0096] In some embodiments, R^x is iPr. In some embodiments,

. In some embodiments, R^x is

. In some embodiments, R^x is . In some embodiments, R^x is

. In some embodiments, R^x is . In some e

some embodiments, R^x is

. , . In some embodiments, R^x is

. In some embodiments, R^x is

. [0097] In certain embodiments, R^x is as depicted in the compounds of Table 2. [0098] As defined about and described herein, R^y is hydrogen, -OR, or R^A. [0099] In some embodiments, R^y is hydrogen. In some embodiments, R^y is -OR. In some embodiments, R^y is R^A. [00100] In some embodiments,

[00101] In certain embodiments, R^y is as depicted in the compounds of Table 2. [00102] As defined about and described herein,

is a warhead group. [00103] In some embodiments, the warhead group is –L²-Y, wherein: L² is a covalent bond or a bivalent C_1-8 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one, two, or three methylene units of L² are optionally and independently replaced by cyclopropylene, —NR—, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO₂—, —SO₂N(R)—, —O—, — C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO₂—, —C(═S)—, —C(═NR)—, —N═N—, or —C(═N₂)—; Y is hydrogen, C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 R^e groups; and each R^e is independently selected from -Q-Z, oxo, NO₂, halogen, CN, a suitable leaving group, or a C_1- ₆ aliphatic optionally substituted with oxo, halogen, NO₂, or CN, wherein: Q is a covalent bond or a bivalent C_1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —SO—, or —SO₂—, — N(R)C(O)—, —C(O)N(R)—, —N(R)SO₂—, or —SO₂N(R)—; and Z is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN. [00104] In certain embodiments, L² is a covalent bond. [00105] In certain embodiments, L² is a bivalent C_1-8 saturated or unsaturated, straight or branched, hydrocarbon chain. In certain embodiments, L² is —CH₂—. [00106] In certain embodiments, L² is a covalent bond, —CH₂—, —NH—, —CH₂NH—, —NHCH₂— , —NHC(O)—, —NHC(O)CH₂OC(O)—, —CH₂NHC(O)—, —NHSO₂—, —NHSO₂CH₂—, — NHC(O)CH₂OC(O)—, or —SO₂NH—. [00107] In some embodiments, L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and one or two additional methylene units of L² are optionally and independently replaced by —NRC(O)—, —C(O)NR—, —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, —C(O)O—, cyclopropylene, —O—, —N(R)—, or —C(O)—. [00108] In certain embodiments, L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —C(O)—, —NRC(O)— , —C(O)NR—, —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, or —C(O)O—, and one or two additional methylene units of L² are optionally and independently replaced by cyclopropylene, —O—, —N(R)—, or —C(O)—. [00109] In some embodiments, L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —C(O)—, and one or two additional methylene units of L² are optionally and independently replaced by cyclopropylene, —O—, — N(R)—, or —C(O)—. [00110] As described above, in certain embodiments, L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond. One of ordinary skill in the art will recognize that such a double bond may exist within the hydrocarbon chain backbone or may be “exo” to the backbone chain and thus forming an alkylidene group. By way of example, such an L² group having an alkylidene branched chain includes —CH₂C(═CH₂)CH₂—. Thus, in some embodiments, L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one alkylidenyl double bond. Exemplary L² groups include —NHC(O)C(═CH₂)CH₂—. [00111] In certain embodiments, L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —C(O)—. In certain embodiments, L² is —C(O)CH═CH(CH₃)—, —C(O)CH═CHCH₂NH(CH₃)—, —C(O)CH═CH(CH₃)—, —C(O)CH═CH—, —CH₂C(O)CH═CH—, —CH₂C(O)CH═CH(CH₃)—, —CH₂CH₂C(O)CH═CH—, — CH₂CH₂C(O)CH═CHCH₂—, —CH₂CH₂C(O)CH═CHCH₂NH(CH₃)—, or — CH₂CH₂C(O)CH═CH(CH3)—, or —CH(CH3)OC(O)CH═CH—. [00112] In certain embodiments, L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —OC(O)—. [00113] In some embodiments, L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —NRC(O)—, —C(O)NR— , —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, or —C(O)O—, and one or two additional methylene units of L² are optionally and independently replaced by cyclopropylene, —O—, — N(R)—, or —C(O)—. In some embodiments, L² is —CH₂OC(O)CH═CHCH₂—, —CH₂— OC(O)CH═CH—, or —CH(CH═CH₂)OC(O)CH═CH—. [00114] In certain embodiments, L² is —NRC(O)CH═CH—, —NRC(O)CH═CHCH₂N(CH₃)—, — NRC(O)CH═CHCH₂O—, —CH₂NRC(O)CH═CH—, —NRSO₂CH═CH—, —NRSO₂CH═CHCH₂—, — NRC(O)(C═N2)C(O)—, —NRC(O)CH═CHCH₂N(CH3)—, —NRSO₂CH═CH—, — NRSO₂CH═CHCH₂—, —NRC(O)CH═CHCH₂O—, —NRC(O)C(═CH₂)CH₂—, —CH₂NRC(O)—, — CH₂NRC(O)CH═CH—, —CH₂CH₂NRC(O)—, or —CH₂NRC(O)cyclopropylene-, wherein each R is independently hydrogen or optionally substituted C_1-6 aliphatic. [00115] In certain embodiments, L² is —NHC(O)CH═CH—, —NHC(O)CH═CHCH₂N(CH3)—, — NHC(O)CH═CHCH₂O—, —CH₂NHC(O)CH═CH—, —NHSO₂CH═CH—, —NHSO₂CH═CHCH₂—, —NHC(O)(C═N2)C(O)—, —NHC(O)CH═CHCH₂N(CH3)—, —NHSO₂CH═CH—, — NHSO₂CH═CHCH₂—, —NHC(O)CH═CHCH₂O—, —NHC(O)C(═CH₂)CH₂—, —CH₂NHC(O)—, — CH₂NHC(O)CH═CH—, —CH₂CH₂NHC(O)—, or —CH₂NHC(O)cyclopropylene-. [00116] In some embodiments, L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one triple bond. In certain embodiments, L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one triple bond and one or two additional methylene units of L² are optionally and independently replaced by —NRC(O)—, —C(O)NR—, —S—, —S(O)—, —SO₂—, —C(═S)—, — C(═NR)—, —O—, —N(R)—, or —C(O)—. In some embodiments, L² has at least one triple bond and at least one methylene unit of L² is replaced by —N(R)—, —N(R)C(O)—, —C(O)—, —C(O)O—, or — OC(O)—, or —O—. [00117] Exemplary L² groups include —C≡C—, —C≡CCH₂N(isopropyl)-, —NHC(O)C≡CCH₂CH₂— , —CH₂—C≡C≡CH₂—, —C≡CCH₂O—, —CH₂C(O)C≡C—, —C(O)C≡C—, or —CH₂OC(═O)C≡C—. [00118] In certain embodiments, L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein one methylene unit of L² is replaced by cyclopropylene and one or two additional methylene units of L² are independently replaced by —C(O)—, —NRC(O)—, —C(O)NR—, —N(R)SO₂—, or —SO₂N(R)—. Exemplary L² groups include —NHC(O)-cyclopropylene-SO₂— and —NHC(O)-cyclopropylene-. [00119] As defined generally above, Y is hydrogen, C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with at 1-4 R^e groups, each R^e is independently selected from -Q-Z, oxo, NO₂, halogen, CN, a suitable leaving group, or C_1-6 aliphatic, wherein Q is a covalent bond or a bivalent C_1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —SO—, or —SO₂—, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO₂—, or —SO₂N(R)—; and, Z is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN. [00120] In certain embodiments, Y is hydrogen. [00121] In certain embodiments, Y is C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN. In some embodiments, Y is C2-6alkenyl optionally substituted with oxo, halogen, NO₂, or CN. In other embodiments, Y is C2-6alkynyl optionally substituted with oxo, halogen, NO₂, or CN. In some embodiments, Y is C2-6alkenyl. In other embodiments, Y is C2-4 alkynyl. [00122] In other embodiments, Y is C_1-6 alkyl substituted with oxo, halogen, NO₂, or CN. Such Y groups include —CH₂F, —CH₂Cl, —CH₂CN, and —CH₂NO₂. [00123] In certain embodiments, Y is a saturated 3-6 membered monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Y is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. [00124] In some embodiments, Y is a saturated 3-4 membered heterocyclic ring having 1 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein. Exemplary such rings are epoxide and oxetane rings, wherein each ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein. [00125] In other embodiments, Y is a saturated 5-6 membered heterocyclic ring having 1-2 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. Such rings include piperidine and pyrrolidine, wherein each ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. In certain embodiments, Y is

wherein each R, Q, Z, and R^e is as defined above and described herein. [00126] In some embodiments, Y is a saturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1-4 R^egroups, wherein each R^e is as defined above and described herein. In certain embodiments, Y is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein each ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. In certain embodiments, Y is

wherein R^e is as defined above and described herein. [00127] In certain embodiments, Y is cyclopropyl optionally substituted with halogen, CN or NO₂. [00128] In certain embodiments, Y is a partially unsaturated 3-6 membered monocyclic ring having 0- 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. [00129] In some embodiments, Y is a partially unsaturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. In some embodiments, Y is cyclopropenyl, cyclobutenyl, cyclopentenyl, or cyclohexenyl wherein each ring is substituted with 1-4 R^e groups, wherein each R^e is as defined 0-3 above and described herein. In certain embodiments,

wherein each R^e is as defined above and described herein. [00130] In certain embodiments, Y is a partially unsaturated 4-6 membered heterocyclic ring having 1- 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. In certain embodiments, Y is selected from:

wherein each R and R^e is as defined above and described herein. [00131] In certain embodiments, Y is a 6-membered aromatic ring having 0-2 nitrogens wherein said ring is substituted with 1-4 R^e groups, wherein each R^e group is as defined above and described herein. In certain embodiments, Y is phenyl, pyridyl, or pyrimidinyl, wherein each ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein. [00132] In some embodiments, Y is selected from:

wherein each R^e is as defined above and described herein. [00133] In other embodiments, Y is a 5-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-3 R^e groups, wherein each R^e group is as defined above and described herein. In some embodiments, Y is a 5 membered partially unsaturated or aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e group is as defined above and described herein. Exemplary such rings are isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyrrolyl, furanyl, thienyl, triazole, thiadiazole, and oxadiazole, wherein each ring is substituted with 1-3 R^e groups, wherein each R^e group is as defined above and described herein. In certain embodiments, Y is selected from:

wherein each R and R^e is as defined above and described herein. [00134] In certain embodiments, Y is an 8-10 membered bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein R^e is as defined above and described herein. According to another aspect, Y is a 9-10 membered bicyclic, partially unsaturated, or aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein R^eis as defined above and described herein. Exemplary such bicyclic rings include 2,3- dihydrobenzo[d]isothiazole, wherein said ring is substituted with 1-4 R^e groups, wherein R^e is as defined above and described herein. [00135] As defined generally above, each R^e group is independently selected from -Q-Z, oxo, NO₂, halogen, CN, a suitable leaving group, or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN, wherein Q is a covalent bond or a bivalent C_1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —SO—, or —SO₂—, —N(R)C(O)—, — C(O)N(R)—, —N(R)SO₂—, or —SO₂N(R)—; and Z is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN. [00136] In certain embodiments, R^e is C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN. In other embodiments, R^e is oxo, NO₂, halogen, or CN. [00137] In some embodiments, R^e is -Q-Z, wherein Q is a covalent bond and Z is hydrogen (i.e., R^e is hydrogen). In other embodiments, R^e is -Q-Z, wherein Q is a bivalent C_1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —NR—, —NRC(O)—, —C(O)NR—, —S—, —O—, —C(O)—, —SO—, or —SO₂—. In other embodiments, Q is a bivalent C2-6 straight or branched, hydrocarbon chain having at least one double bond, wherein one or two methylene units of Q are optionally and independently replaced by —NR—, — NRC(O)—, —C(O)NR—, —S—, —O—, —C(O)—, —SO—, or —SO₂—. In certain embodiments, the Z moiety of the R^e group is hydrogen. In some embodiments, -Q-Z is —NHC(O)CH═CH₂ or — C(O)CH═CH₂. [00138] In certain embodiments, each R^e is independently selected from oxo, NO₂, CN, fluoro, chloro, —NHC(O)CH═CH₂, —C(O)CH═CH₂, —CH₂CH═CH₂, —C≡CH, —C(O)OCH₂Cl, —C(O)OCH₂F, — C(O)OCH₂CN, —C(O)CH₂Cl, —C(O)CH₂F, —C(O)CH₂CN, or —CH₂C(O)CH3. _[00139] In certain embodiments, R^e is a suitable leaving group, i.e., a group that is subject to nucleophilic displacement. A “suitable leaving” is a chemical group that is readily displaced by a desired incoming chemical moiety such as the thiol moiety of a cysteine of interest. Suitable leaving groups are well known in the art, e.g., see, “Advanced Organic Chemistry,” Jerry March, 5^th Ed., pp. 351-357, John Wiley and Sons, N.Y. Such leaving groups include, but are not limited to, halogen, alkoxy, sulphonyloxy, optionally substituted alkylsulphonyloxy, optionally substituted alkenylsulfonyloxy, optionally substituted arylsulfonyloxy, acyl, and diazonium moieties. Examples of suitable leaving groups include chloro, iodo, bromo, fluoro, acetoxy, methanesulfonyloxy (mesyloxy), tosyloxy, triflyloxy, nitro-phenylsulfonyloxy (nosyloxy), and bromo-phenylsulfonyloxy (brosyloxy). [00140] In certain embodiments, the following embodiments and combinations of - L²-Y apply: (a) L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and one or two additional methylene units of L² are optionally and independently replaced by — NRC(O)—, —C(O)NR—, —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, — C(O)O—, cyclopropylene, —O—, —N(R)—, or —C(O)—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (b) L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —C(O)—, —NRC(O)—, —C(O)NR—, — N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, or —C(O)O—, and one or two additional methylene units of L² are optionally and independently replaced by cyclopropylene, —O— , —N(R)—, or —C(O)—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (c) L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —C(O)—, and one or two additional methylene units of L² are optionally and independently replaced by cyclopropylene, —O—, —N(R)—, or — C(O)—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (d) L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —C(O)—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (e) L² is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L² has at least one double bond and at least one methylene unit of L² is replaced by —OC(O)—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (f) L² is —NRC(O)CH═CH—, —NRC(O)CH═CHCH₂N(CH3)—, —NRC(O)CH═CHCH₂O—, — CH₂NRC(O)CH═CH—, —NRSO₂CH═CH—, —NRSO₂CH═CHCH₂—, —NRC(O)(C═N2)—, — NRC(O)(C═N2)C(O)—, —NRC(O)CH═CHCH₂N(CH3)—, —NRSO₂CH═CH—, — NRSO₂CH═CHCH₂—, —NRC(O)CH═CHCH₂O—, —NRC(O)C(═CH₂)CH₂—, —CH₂NRC(O)—, —CH₂NRC(O)CH═CH—, —CH₂CH₂NRC(O)—, or —CH₂NRC(O)cyclopropylene-; wherein R is H or optionally substituted C_1-6 aliphatic; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (g) L² is —NHC(O)CH═CH—, —NHC(O)CH═CHCH₂N(CH3)—, —NHC(O)CH═CHCH₂O—, — CH₂NHC(O)CH═CH—, —NHSO₂CH═CH—, —NHSO₂CH═CHCH₂—, —NHC(O)(C═N2)—, — NHC(O)(C═N2)C(O)—, —NHC(O)CH═CHCH₂N(CH3)—, —NHSO₂CH═CH—, — NHSO₂CH═CHCH₂—, —NHC(O)CH═CHCH₂O—, —NHC(O)C(═CH₂)CH₂—, —CH₂NHC(O)—, —CH₂NHC(O)CH═CH—, —CH₂CH₂NHC(O)—, or —CH₂NHC(O)cyclopropylene-; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (h) L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one alkylidenyl double bond and at least one methylene unit of L² is replaced by —C(O)—, —NRC(O)—, — C(O)NR—, —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, or —C(O)O—, and one or two additional methylene units of L² are optionally and independently replaced by cyclopropylene, —O—, —N(R)—, or —C(O)—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (i) L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein L² has at least one triple bond and one or two additional methylene units of L² are optionally and independently replaced by —NRC(O)— , —C(O)NR—, —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, or — C(O)O—, and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (j) L² is —C≡C—, —C≡CCH₂N(isopropyl)-, —NHC(O)C≡CCH₂CH₂—, —CH₂—C≡C≡CH₂—, — C≡CCH₂O—, —CH₂C(O)C≡C—, —C(O)C≡C—, or —CH₂C(═O)C≡C—; and Y is hydrogen or C_1- ₆ aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (k) L² is a bivalent C_2-8 straight or branched, hydrocarbon chain wherein one methylene unit of L² is replaced by cyclopropylene and one or two additional methylene units of L² are independently replaced by — NRC(O)—, —C(O)NR—, —N(R)SO₂—, —SO₂N(R)—, —S—, —S(O)—, —SO₂—, —OC(O)—, or —C(O)O—; and Y is hydrogen or C_1-6 aliphatic optionally substituted with oxo, halogen, NO₂, or CN; or (l) L² is a covalent bond and Y is selected from: (i) C_1-6 alkyl substituted with oxo, halogen, NO₂, or CN; (ii) C2-6alkenyl optionally substituted with oxo, halogen, NO₂, or CN; or (iii) C2-6alkynyl optionally substituted with oxo, halogen, NO₂, or CN; or (iv) a saturated 3-4 membered heterocyclic ring having 1 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein; or (v) a saturated 5-6 membered heterocyclic ring having 1-2 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (

wherein each R, Q, Z, and R^e is as defined above and described herein; or (vii) a saturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (viii) a partially unsaturated 3-6 membered monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (ix) a partially unsaturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1- 4 R^egroups, wherein each R^e is as defined above and described herein; or

(x) wherein each R^e is as defined above and described herein; or (xi) a partially unsaturated 4-6 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (

wherein each R and R^e is as defined above and described herein; or (xiii) a 6-membered aromatic ring having 0-2 nitrogens wherein said ring is substituted with 1-4 R^egroups, wherein each R^e group is as defined above and described herein; or (

wherein each R^e is as defined above and described herein; or (xv) a 5-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-3 R^egroups, wherein each R^e group is as defined above and described herein; or

(xvi)

wherein each R and R^e is as defined above and described herein; or (xvii) an 8-10 membered bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein R^e is as defined above and described herein; (m) L² is —C(O)— and Y is selected from: (i) C_1-6 alkyl substituted with oxo, halogen, NO₂, or CN; or (ii) C_2-6alkenyl optionally substituted with oxo, halogen, NO₂, or CN; or (iii) C_2-6alkynyl optionally substituted with oxo, halogen, NO₂, or CN; or (iv) a saturated 3-4 membered heterocyclic ring having 1 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein; or (v) a saturated 5-6 membered heterocyclic ring having 1-2 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (

wherein each R^e is as defined above and described herein; or (xi) a partially unsaturated 4-6 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (

wherein each R^e is as defined above and described herein; or (xv) a 5-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-3 R^egroups, wherein each R^e group is as defined above and described herein; or (

wherein each R and R^e is as defined above and described herein; or (xvii) an 8-10 membered bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein R^e is as defined above and described herein; (n) L² is —N(R)C(O)— and Y is selected from: (i) C_1-6 alkyl substituted with oxo, halogen, NO₂, or CN; or (ii) C2-6alkenyl optionally substituted with oxo, halogen, NO₂, or CN; or (iii) C2-6alkynyl optionally substituted with oxo, halogen, NO₂, or CN; or (iv) a saturated 3-4 membered heterocyclic ring having 1 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein; or (v) a saturated 5-6 membered heterocyclic ring having 1-2 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or ( wherein each R, Q, Z, a ^e

nd R is as defined above and described herein; or (vii) a saturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (viii) a partially unsaturated 3-6 membered monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (ix) a partially unsaturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1- 4 R^egroups, wherein each R^e is as defined above and described herein; or (x) , wherein each R^e is as defined above and described herein; or (xi) a partially unsaturated 4-6 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (xii)

, wherein each R and R^e is as defined above and described herein; or (xiii) a 6-membered aromatic ring having 0-2 nitrogens wherein said ring is substituted with 1-4 R^egroups, wherein each R^e group is as defined above and described herein; or (

wherein each R and R^e is as defined above and described herein; or (xvii) an 8-10 membered bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^egroups, wherein R^e is as defined above and described herein; (o) L² is a bivalent C_1-8 saturated or unsaturated, straight or branched, hydrocarbon chain; and Y is selected from: (i) C_1-6 alkyl substituted with oxo, halogen, NO₂, or CN; (ii) C_2-6alkenyl optionally substituted with oxo, halogen, NO₂, or CN; or (iii) C_2-6alkynyl optionally substituted with oxo, halogen, NO₂, or CN; or (iv) a saturated 3-4 membered heterocyclic ring having 1 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein; or (v) a saturated 5-6 membered heterocyclic ring having 1-2 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or ( ^e

wherein each R, Q, Z, and R is as defined above and described herein; or (vii) a saturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (viii) a partially unsaturated 3-6 membered monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (ix) a partially unsaturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1- 4 R^egroups, wherein each R^e is as defined above and described herein; or

R and R^e is as defined above and described herein; or (xiii) a 6-membered aromatic ring having 0-2 nitrogens wherein said ring is substituted with 1-4 R^egroups, wherein each R^e group is as defined above and described herein; or (

wherein each R and R^e is as defined above and described herein; or (xvii) an 8-10 membered bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^egroups, wherein R^e is as defined above and described herein; (p) L² is a covalent bond, —CH₂—, —NH—, —C(O)—, —CH₂NH—, —NHCH₂—, —NHC(O)—, — NHC(O)CH₂OC(O)—, —CH₂NHC(O)—, —NHSO₂—, —NHSO₂CH₂—, —NHC(O)CH₂OC(O)—, or —SO₂NH—; and Y is selected from: (i) C_1-6 alkyl substituted with oxo, halogen, NO₂, or CN; or (ii) C2-6alkenyl optionally substituted with oxo, halogen, NO₂, or CN; or (iii) C2-6alkynyl optionally substituted with oxo, halogen, NO₂, or CN; or (iv) a saturated 3-4 membered heterocyclic ring having 1 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-2 R^e groups, wherein each R^e is as defined above and described herein; or (v) a saturated 5-6 membered heterocyclic ring having 1-2 heteroatom selected from oxygen or nitrogen wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or wherei ^e

n each R, Q, Z, and R is as defined above and described herein; or (vii) a saturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (viii) a partially unsaturated 3-6 membered monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein each R^e is as defined above and described herein; or (ix) a partially unsaturated 3-6 membered carbocyclic ring, wherein said ring is substituted with 1- 4 R^egroups, wherein each R^e is as defined above and described herein; or

wherein each R and R^e is as defined above and described herein; or (xiii) a 6-membered aromatic ring having 0-2 nitrogens wherein said ring is substituted with 1-4 R^egroups, wherein each R^e group is as defined above and described herein; or (xiv)

wherein each R and R^e is as defined above and described herein; or (xvii) an 8-10 membered bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R^e groups, wherein R^e is as defined above and described herein. [00141] In certain embodiments, the Y group is selected from those set forth in Table 1A below, wherein each wavy line indicates the point of attachment to the rest of the molecule. Table 1A. Exemplary Y groups

wherein each R^e is independently a suitable leaving group, NO₂, CN or oxo. [00142] In certain embodiments, a warhead group is —C≡CH, —C≡CCH₂NH(isopropyl), — NHC(O)C≡CCH₂CH3, —CH₂—C≡C≡CH3, —C≡CCH₂OH, —CH₂C(O)C≡CH, —C(O)C≡CH, or — CH₂C(═O)C≡CH. In some embodiments, R¹ is selected from —NHC(O)CH═CH₂, — NHC(O)CH═CHCH₂N(CH3)₂, or —CH₂NHC(O)CH═CH₂. [00143] In certain embodiments, a warhead group is selected from those set forth in Table 1B, below, wherein each wavy line indicates the point of attachment to the rest of the molecule. Table 1B. Exemplary Warhead Groups

wherein each R^e is independently a suitable leaving group, NO₂, CN, or oxo. [00144] In some embodiments, Y of a warhead group is an isoxazoline compound or derivative capable of covalently binding to serine. In some embodiments, Y of a warhead group is an isoxazoline compound or derivative described in WO 2010135360, the entire content of which is incorporated herein by reference. As understood by one skilled in the art, an isoxazoline compound or derivative described in WO 2010135360, as Y of a warhead group, can covalently connect to L² of the warhead group at any reasonable position of the isoxazoline compound or derivative. In some embodiments, Y of a warhead group is:

wherein G, R^a, and R^c are:

[00145] In some embodiments, the warhead group is an aldehyde. [00146] In some embodiments, the warhead group is an oxime or derivative thereof. In some embodiments, the oxime i

wherein R is defined above and described herein. [00147] In some embodiments, the warhead group is a nitroalkene. In some embodiments, the nitroalkene is

[00148] In some embodiments, the warhead group is

. In some embodiments, the warhead group is

. [00149] In some embodiments, the warhead group is

. In some embodiments, the warhead group is

. , . In some embodiments, the

warhead group is . In some embodiments, the warhead group is . In some embodiments, the warhead group is

. In some embodiments, the warhead group is

. [00150] In some embodiments, the warhead group is:

wherein each of the variables Het, R4, and R5 is as defined and described in US6420364, the entirety of each of which is herein incorporated by reference. [00151] In some embodiments, the warhead group is a reversible cysteine protease inhibitor:

wherein each of the variables X, R1, R2, R3, and R4 is as defined and described in WO1996040737 and US6030946, the entirety of each of which is herein incorporated by reference. [00152] In certain embodiments, the warhead group is as depicted in the compounds of Table 2.

. [00154] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaa-6 or I-aaa-7:

I-aaa-7 or a pharmaceutically acceptable salt thereof, wherein L, DIM, and

are as defined above and described in embodiments herein, and wherein each of the variables R¹, R², R³, R⁴, and R⁵ is as defined and described in WO₂020030143, the entirety of each of which is herein incorporated by reference. [00155] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-bbb:

I-bbb or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, and is as defined and described in KR101128088, the entirety of each of which is herein incorporated by reference. [00156] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ccc:

or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R, R1, and Ar is as defined and described in CN1699354 and CN1699355, the entirety of each of which is herein incorporated by reference. [00157] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ddd:

I-ddd or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R¹, R², and R³ is as defined and described in US7662860, the entirety of each of which is herein incorporated by reference. [00158] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-eee:

I-eee or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R₁, X, Y, and Z is as defined and described in US6004933, the entirety of each of which is herein incorporated by reference. [00159] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-fff:

I-fff or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables M, R₁, R₂, R₃, R₅, R₆, R₇, R₂₀, Z, and Z₁ is as defined and described in US20040235952, the entirety of each of which is herein incorporated by reference. [00160] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ggg:

I-ggg or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R₂, R₅, R₆, R₇, A, Z, and Y is as defined and described in US7504382, the entirety of each of which is herein incorporated by reference. [00161] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-hhh-1, I-hhh-2, I-hhh- 3, I-hhh-4, or I-hhh-5:

I-hhh-5 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, P, Q, U, V, W, X, Y, Z, l, m, and n is as defined and described in US2005267071, the entirety of each of which is herein incorporated by reference. [00162] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-iii-1 to I-iii-4:

I-iii-4 or a pharmaceutically acceptable salt thereof, wherein L, DIM, and

are as defined above and described in embodiments herein, and wherein each of the variables R and R¹ is as defined and described in US2006014821, the entirety of each of which is herein incorporated by reference. [00163] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-jjj: A1-L-A2 I-jjj or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables A1, A2, and L is as defined and described in US2006019967, the entirety of each of which is herein incorporated by reference. [00164] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-kkk:

I-kkk or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, and A is as defined and described in WO₂006095624, the entirety of each of which is herein incorporated by reference. [00165] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-lll:

I-lll or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, R4, R5, R6, R7, X, Y, m, n, m’, and n’ is as defined and described in US8648076, the entirety of each of which is herein incorporated by reference. [00166] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-mmm:

I-mmm or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R11, R12, R13, R14, R15, R21, R22, R23, R24, R25, and Q is as defined and described in CN100502868, the entirety of each of which is herein incorporated by reference. [00167] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-nnn:

I-nnn or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R3, R4, R5, R6, T, U, V, W, X, Het1, Ru, Rv, and Rw is as defined and described in US7462615, the entirety of each of which is herein incorporated by reference. [00168] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ooo-1, I-ooo-2, I-ooo- 3, I-ooo-4, I-ooo-5, or I-ooo-6:

I-ooo-1

I-ooo-6 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables J, Q, Y, Z, W, E1, T, X, Z, and M is as defined and described in US20070149487, the entirety of each of which is herein incorporated by reference. [00169] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ppp:

I-ppp or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables A, X, Y, and Z is as defined and described in KR101054464, the entirety of each of which is herein incorporated by reference. [00170] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-qqq:

I-qqq or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, R3’, R4, R4’, R5, Ar1, Ar2, X, n, and m is as defined and described in WO₂010081783, the entirety of each of which is herein incorporated by reference. [00171] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-rrr:

I-rrr or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, and X is as defined and described in WO₂013014074, the entirety of each of which is herein incorporated by reference. [00172] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-rrr-1:

I-rrr-1 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, and X is as defined and described in CN104069090, the entirety of each of which is herein incorporated by reference. [00173] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-rrr-2:

I-rrr-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1 and R2 is as defined and described in CN103230393, the entirety of each of which is herein incorporated by reference. [00174] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-sss-1 or I-sss-2:

I-sss-2 or a pharmaceutically acceptable salt thereof, wherein L, DIM, and

are as defined above and described in embodiments herein, and wherein each of the variables R0, R1, and Z is as defined and described in US9474759, the entirety of each of which is herein incorporated by reference. [00175] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ttt-1 and I-ttt-2:

I-ttt-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R⁰, R¹, R², R³, X, Y, and Z is as defined and described in US9309284, the entirety of each of which is herein incorporated by reference. [00176] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-uuu:

I-uuu or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, R4, R5, R5’, R6, X1, X2, n, and m is as defined and described in US10000495, the entirety of each of which is herein incorporated by reference. [00177] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-vvv-1 or I-vvv-2:

I-vvv-2 or a pharmaceutically acceptable salt thereof, wherein L, DIM, and

are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, R₃, X, and U is as defined and described in CN105837487, the entirety of each of which is herein incorporated by reference. [00178] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-www:

I-www or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables Ri, Rj, Rk, X, Y, Z, i, j, k, n, and n’ is as defined and described in US9328093, the entirety of each of which is herein incorporated by reference. [00179] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-xxx-1 or I-xxx-2:

I-xxx-1

I-xxx-2 or a pharmaceutically acceptable salt thereof, wherein L, DIM, and

are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, X, Y, and n is as defined and described in WO₂017114509, the entirety of each of which is herein incorporated by reference. [00180] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-yyy-1, I-yyy-2, or I- yyy-3:

I-yyy-3 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, R₃, Q, X, Y, Z, m, and n is as defined and described in WO₂017222935, the entirety of each of which is herein incorporated by reference. [00181] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-zzz-1, I-zzz-2, or I- zzz-3:

I-zzz-1

I-zzz-2

I-zzz-3 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R, R1, R2, Z, and “recognition element” is as defined and described in US2019151400, the entirety of each of which is herein incorporated by reference. [00182] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-aaaa-1 or I-aaaa-2:

I-aaaa-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R8’, and X is as defined and described in US7462594 and US7304088, the entirety of each of which is herein incorporated by reference. [00183] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-bbbb:

I-bbbb or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R¹, R³, R⁴, R⁵, and R⁶ is as defined and described in US9975885, the entirety of each of which is herein incorporated by reference. [00184] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-cccc-1 to I-cccc-4:

I-cccc-3

I-cccc-4 or a pharmaceutically acceptable salt thereof, wherein L, DIM, and

are as defined above and described in embodiments herein, and wherein each of the variables Ring A, R¹, R’¹, R”¹, R², R³, R⁴, and R⁵ is as defined and described in WO₂018042343, the entirety of each of which is herein incorporated by reference. [00185] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-dddd-1 or I-dddd-2:

I-dddd-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables W, R₁, R₂, R₃, and R₄ is as defined and described in WO₂005080353, the entirety of each of which is herein incorporated by reference. [00186] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-eeee-1 or I-eeee-2:

I-eeee-1

I-eeee-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R², A, E, X, Y, m, and Z is as defined and described in WO₂006061714, the entirety of each of which is herein incorporated by reference. [00187] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-ffff-1 or I-ffff-2:

I-ffff-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R², A, B, X, Y, m, and Z is as defined and described in WO₂005113580, the entirety of each of which is herein incorporated by reference. [00188] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-gggg-1 or I-gggg-2:

I-gggg-1

I-gggg-2 or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein each of the variables R1, R2, R3, and R4 is as defined and described in St. John et al., Bioorg. Med. Chem. 2015, 23:6036, the entirety of each of which is herein incorporated by reference. [00189] In certain embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety thereby forming a compound of formula I-hhhh:

or a pharmaceutically acceptable salt thereof, wherein L and DIM are as defined above and described in embodiments herein, and wherein R is as defined and described in Turlington et al., Bioorg. Med. Chem. Lett.2013, 23:6172, the entirety of each of which is herein incorporated by reference. [00190] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in KR101612051, for example: ,

a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon or oxygen atom. [00191] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in KR101418898 and KR20120081768, for example, compounds 1 to 45, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00192] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in KR20110086473, for example, a compound extracted from ecklonia cava, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00193] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Appleyard and Tisdale, J. Gen. Virol.1985, 66:363, for example, leupeptin, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00194] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Liu and Wang, J. Genetics and Genomics 2020, 47:119, for example, a compound named in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00195] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Collins and Grubb, Oral Microbiol. Immunol. 1998, 13:59, for example, cystatin D, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00196] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Bacha et al., Biochemistry 2004, 43:4906, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00197] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Tan et al., Emerging Infectious Diseases 2004, 10(4):581, for example, an antiviral drug in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00198] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Yamamoto et al., Biochem. Biophys. Res. Comm.2004, 318:719, for example, nelfinavir, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00199] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Rahnarayanon et al., Biochem. Biophys. Res. Comm. 2004, 321:370, for example, compounds 1 to 15 in Figure 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00200] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in US2007015815, for example, a mentioned hydrazide drug, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00201] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kao et al., FEBS Letters. 2004, 576:325, for example, compounds A to D in Figure 4, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00202] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Lin et al., Antivir. Res.2005, 68:36, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00203] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kaeppler et al., J. Med. Chem. 2005, 48(22):6832, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00204] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Yang et al., PLOS Biology 2005, 3(10):1742, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00205] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Martina et al., Bioorg. Med. Chem. Lett. 2005, 15:5365, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00206] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Zhou et al., J. Med. Chem. 2006, 49(12):3440, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00207] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Tsai et al., J. Med. Chem. 2006, 49(12):3485, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein is attached to a

modifiable carbon, nitrogen, or oxygen atom. [00208] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Al-Gharabli et al., ChemBioChem. 2006, 7:1048, for example, a compound in Table 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00209] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Lu et al., J. Med. Chem. 2006, 49(17):5154, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00210] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Sararino et al., Expert Opin. Ther. Patents 2006, 16(9):1269, for example, compound 1 to 98, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00211] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Chen et al., Bioorg. Med. Chem. 2006, 14:8295, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00212] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Zhang et al., J. Med. Chem. 2007, 30(8):1850, for example, compound 7, 11, 12, 16, 17-47, and 53-57, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00213] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Goetz et al., Biochemistry 2007, 46:8744, for example, a compound in Figure 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00214] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ghosh et al., Bioorg. Med. Chem. Lett. 2007, 17:5876, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00215] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Bacha et al., Chem. Biol. Drug. Des.2008, 72:34, for example, a compound in Table 5, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00216] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Chen et al., Anal. Chem. Chemother. 2008, 19:151, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon or nitrogen atom. [00217] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ghosh et al., J. Med. Chem. 2010, 53(13):59, for example, a compound in Table1-2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00218] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Nguyen et al., Biotechnol. Lett.2012, 34:831, for example, a compound in Figure 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00219] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Park et al., Bioorg. Med. Chem.2012, 20:5928, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00220] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kim et al., J. Virol. 2012, 86(21):11754, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00221] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Park et al., Biol. Pharm. Bull 2012, 35(11):2036, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00222] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Chuck et al., Eur. J. Med. Chem.2013, 59:1, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00223] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kim et al., Antivir. Res.2013, 97:161, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00224] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Cho et al., Bioorg. Med. Chem.2013, 21:3051, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00225] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Lee et al., ChemMedChem. 2013, 8:1361, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein is attached to a

modifiable carbon, nitrogen, or oxygen atom. [00226] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kumar et al., Expert Opin. Ther. Patents 2013, 23(10):1337, for example, compound 1 to 98, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00227] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Prior et al., Bioorg. Med. Chem. Lett. 2013, 23:56317, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00228] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Liu et al., Bioorg. Med. Chem. 2014, 22:292, for example, a compound in Table 1-3, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00229] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Lee et al., Bioorg. Med. Chem. 2014, 22:167, for example, a compound in Figure 5, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00230] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kim et al., J. Enzyme Inhib. Med. Chem. 2014, 29(1):59, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon or oxygen atom. [00231] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Baez-Santos et al., J. Med. Chem. 2014, 57:2393, for example, a compound in Table 1 or 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein attached to a modifiable carbon, nitrogen, or oxygen atom.

[00232] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Song et al., Biol. Pharm. Bull 2014, 37(6):1021, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00233] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Cheng et al., Antivir. Res. 2015, 115:9, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00234] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Baez-Santos et al., Antivir. Res.2015, 115:21, for example, a compound in Figure 8-10, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00235] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kim et al., J. Virol. 2015, 89(9):4942, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00236] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in St. John et al., Bioorg. Med. Chem. 2015, 23:6036, for example, a compound in Table 1a and 1b, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

attached to a modifiable carbon, nitrogen, or oxygen atom. [00237] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kumar et al., Bioorg. Med. Chem. 2015, 24:6035, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00238] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Teruya et al., Biopolymers 2015, 106(4):391, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00239] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in CN106166153, for example, compound 1-13, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00240] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Park et al., J. Enzyme Inhib. Med. Chem. 2017, 32(1):504, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon or oxygen atom. [00241] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kumar et al., Antivir. Res. 2017, 141:101, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein is attached to a modifiable carbon or oxygen atom. [00242] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Wang et al., Eur. J. Med. Chem. 2017, 137:450, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon or oxygen atom. [00243] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in KR101934199, for example, a compounds PL-1 to 6, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00244] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kankanamalage et al., Eur. J. Med. Chem. 2018, 150:334, for example, a compounds in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00245] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Perera et al., Antivir. Res. 2018, 160:79, for example, a compounds in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00246] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Rabaan et al., J. Med. Microbiol. 2017, 66:1261, for example, a small molecule therapy in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00247] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Wu et al., Eur. J. Med. Chem. 2019, 167:472, for example, a compound in Table 6, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00248] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Shie et al., J. Med. Chem. 2005, 48(13):4469, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00249] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Chen et al., Bioorg. Med. Chem. Lett. 2005, 15:3058, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00250] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Shie et al., Bioorg. Med. Chem. 2005, 13:5240, for example, a compound in Table 1 or 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00251] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ghosh et al., J. Med. Chem. 2005, 48(22):6768, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00252] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Wu et al., Chem. Biol.2005, 13:261, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

s attached to a modifiable carbon, nitrogen, or oxygen atom. [00253] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Liang, Curr. Top. Med. Chem. 2006, 6:361, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00254] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Yang et al., J. Med. Chem. 2006, 49:4971, for example, a compound in Table 1 or 3, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00255] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Sydnes et al., Tetrahedron 2006, 62:8601, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00256] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in de Lira et al., J. Braz. Chem. Soc.2007, 18(2):440, for example, a compound in Scheme 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00257] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Wen et al., J. Med. Chem. 2007, 50(17):4087, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00258] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Shao et al., Bioorg. Med. Chem. 2008, 16:4652, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00259] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Akaji et al., Bioorg. Med. Chem. 2008, 16:9400, for example, a compound in Table 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00260] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ratia et al., PNAS 2008, 105(42):16119, for example, a compound in Figure 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein is attached to a

modifiable carbon, nitrogen, or oxygen atom. [00261] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Yang et al., Chem. Pharm. Bull.2008, 56(10):1400, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00262] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Regnier et al., Bioorg. Med. Chem. 2009, 19:2722, for example, a compound in Table 1 or 2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00263] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ahn et al., Bull. Korean Chem. Soc. 2010, 31(1):87, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00264] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ramajayam et al., Bioorg. Med. Chem. 2010, 18:7849, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00265] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ramajayam et al., Biochem. Soc. Trans. 2011, 39(5):1371, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00266] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Shao et al., J. Med. Chem.. 2012, 8:1654, for example, a compound in Scheme 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00267] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Jacobs et al., J. Med. Chem. 2013, 56:534, for example, a compound in Figure 1-5, 8, 9, Scheme 1, or Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00268] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Konno et al., Bioorg. Med. Chem.2013, 21:412, for example, a compound in Table 1-3, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein is attached to a

modifiable carbon, nitrogen, or oxygen atom. [00269] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Thanigaimalai et al., Eur. J. Med. Chem. 2013, 68:372, for example, a compound in Figure 1 or Table 1-2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00270] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Shimamoto et al., Bioorg. Med. Chem. 2015, 23:876, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00271] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Konno et al., Bioorg. Med. Chem.2016, 24:1241, for example, a compound in Table 1-6, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00272] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Kim et al., J. Enzyme Inhib. Med. Chem. 2020, 35(1):145, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00273] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Yoshizawa et al., Bioorg. Med. Chem.2020, 28(4):115273, for example, a compound in Table 1 or 3, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00274] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Rani et al., ChemRxiv 2020, https://doi.org/10.26434/chemrxiv.12030345.v1, for example, a compound in Table 3, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00275] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Zhavoronkov et al., Bioorg. Med. Chem. 2020, 28(4):115273, for example, a compound in Figure 4 or 5, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00276] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Xi, Kai. (2009) Total Synthesis of Platensimycin and Platencin and Design and Synthesis of SARS Coronavirus Chymotrypsin- Like Protease Inhibitors, Doctoral Dissertation, Purdue University, for example, a compound in Table 3.2, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00277] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Tong, T. R., Recent Patents on Anti-Infective Drug Discovery 2006, 1:297, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00278] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Yang et al., Curr. Pharma. Design 2006, 12:4573, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00279] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Zhao et al., Recent Patents on Anti-Infective Drug Discovery 2013, 8:150, for example, a compound in Figure 3-5, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00280] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Tong, T. R., Frontiers in Anti- Infective Drug Discovery 2010, 1:83, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00281] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Pillaiyar et al., J. Med. Chem. 2016, 59:6595, for example, any one of compounds 1-186 in Figure 5, 7, 9, 11, 13-27, 29, 30, 32-36, or Table 3-7, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00282] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Zhang et al., J. Med. Chem. 2020, https://doi.org/10.1021/acs.jmedchem.9b01828, for example, a compound in Table 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00283] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Zhang et al., Science 2020, 10.1126/science.abb3405, for example, a compound in Figure 1, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. [00284] In some embodiments, the present invention provides a compound of formula I, wherein PBM is a coronavirus protease binding moiety selected from a compound recited in Ghosh et al., ChemMedChem 2020, doi: 10.1002/cmdc.202000223, for example, a compound in Figure 2, 3, 6, 7, 9, 10, 12-17, 19, 20, 22-30, 32, and 33, or a pharmaceutically acceptable salt thereof, the entirety of each of which is herein incorporated by reference, wherein

is attached to a modifiable carbon, nitrogen, or oxygen atom. Ligase Binding Moiety (LBM) [00285] In some embodiments, LBM is an E3 ligase ligand well known to one of ordinary skill in the art including those described in M. Toure, C. M. Crews, Angew. Chem. Int. Ed. 2016, 55, 1966, T. Uehara et al. Nature Chemical Biology 2017, 13, 675, WO 2017/176708, US 2017/0281784, WO 2017/161119, WO 2017/176957, WO 2017/176958, WO 2015/160845, US 2015/0291562, WO 2016/197032, WO 2016/105518, US 2018/0009779, WO 2017/007612, 2018/0134684, WO 2013/106643, US 2014/0356322, WO 2002/020740, US 2002/0068063, WO 2012/078559, US 2014/0302523, WO 2012/003281, US 2013/0190340, US 2016/0022642, WO 2014/063061, US 2015/0274738, WO 2016/118666, US 2016/0214972, WO 2016/149668, US 2016/0272639, WO 2016/169989, US 2018/0118733, WO 2016/197114, US 2018/0147202, WO 2017/011371, US 2017/0008904, WO 2017/011590, US 2017/0037004, WO 2017/079267, US 2017/0121321, WO 2017/117473, WO 2017/117474, WO 2013/106646, WO 2014/108452, WO 2017/197036, US 2019/0076540, WO 2017/197046, US 2019/0076542, WO 2017/197051, US 2019/0076539, WO 2017/197055, US 2019/0076541, and WO 2017/197056, the entirety of each of which is herein incorporated by reference. [00286] As defined herein and described below, wherein a formula is depicted using square brackets, e..g,

, L is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom within DIM or LBM including substitution or replacement of a defined group in DIM or LBM. [00287] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a cereblon E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-a:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF3–, –SO₂–, –S(O)–, –P(O)R–, – P(O)OR–, –P(O)NR₂–, –C(O)–, –C(S)–, or

X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR₂–, –NR–, –O–, –S–, or –Si(R₂)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, –P(O)(OR)₂, – P(O)(NR₂)OR, –P(O)(NR₂)₂, –Si(OH)₂R, –Si(OH)(R)₂, –Si(R)₃, or an optionally substituted C_1-4 aliphatic; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R;

, , , , ,

Ring B is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; R³ is selected from hydrogen, halogen, –OR, –N(R)₂, or –SR; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or –N(R)S(O)₂R; R⁵ is hydrogen, C1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; m is 0, 1, 2, 3 or 4; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. _[00288] Where a point of attachment of –(R²)_m is depicted on Ring B, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be on Ring A and may also be at any available carbon or nitrogen atom on Ring A including the ring to which Ring B is fused. Where - R² is attached to a nitrogen atom bound to R⁴ or R⁵, R⁴ or R⁵ is absent and -R² takes the place of the R⁴ or R⁵ group. Where -R² is attached to a carbon atom bound to R³, R³ is absent and -R² takes the place of the R³ group. [00289] In some embodiments, a compound of formula I-a above is provided as a compound of formula I-aʹ or formula I-aʹʹ:

I-aʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring A, L, L¹, R¹, R², X¹, X², X³, and m is as defined above. [00290] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-b:

I-b or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF3–, –SO₂–, –S(O) –, –P(O)R–, –

X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR₂–, –NR–, –O–, –S–, or –Si(R₂)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, –P(O)(OR)₂, – P(O)(NR₂)OR, –P(O)(NR₂)₂, –Si(OH)₂R, –Si(OH)(R)₂, -Si(R)₃, or an optionally substituted C_1-4 aliphatic; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)( P(O)(NR₂)₂, or –N(R)S(O)₂R; Ring A is a bi- or tricyclic ring selected from

wherein Ring B is other than imidazo or benzo,

wherein Ring B is other than benzo,

, , , , ,

wherein Ring B is other than benzo,

,

Ring B is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; R³ is selected from hydrogen, halogen, –OR, –N(R)₂, or –SR; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or –N(R)S(O)₂R; R⁵ is hydrogen, C1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3 or 4; and each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00291] Where a point of attachment of –(R²)m is depicted on Ring B, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)m may be on Ring A and may also be at any available carbon or nitrogen atom on Ring A including the ring to which Ring B is fused. Where - R² is attached to a nitrogen atom bound to R⁴ or R⁵, R⁴ or R⁵ is absent and -R² takes the place of the R⁴ or R⁵ group. Where -R² is attached to a carbon atom bound to R³, R³ is absent and -R² takes the place of the R³ group. [00292] In some embodiments, the compound of formula I-b above is provided as a compound of formula I-bʹ or formula I-bʹʹ:

or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring A, L, R¹, R², X¹, X², X³, and m is as defined above. [00293] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-c:

I-c or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR2, or an optionally substituted C1-4 aliphatic; each R² is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R;

Ring B is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; R³ is selected from hydrogen, halogen, –OR, –N(R)₂, or –SR; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R; R⁵ is hydrogen, C1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3 or 4; and each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00294] Where a point of attachment of –(R²)m is depicted on Ring B, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)m may be on Ring A and may also be at any available carbon or nitrogen atom on Ring A including the ring to which Ring B is fused. Where - R² is attached to a nitrogen atom bound to R⁴ or R⁵, R⁴ or R⁵ is absent and -R² takes the place of the R⁴ or R⁵ group. Where -R² is attached to a carbon atom bound to R³, R³ is absent and -R² takes the place of the R³ group. [00295] In some embodiments, the compound of formula I-c above is provided as a compound of formula I-cʹ or formula I-cʹʹ:

I-cʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring A, L, R¹, R², X¹, and m is as defined above. [00296] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-d:

or a pharmaceutically acceptable salt thereof, wherein, L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF₃–, –SO₂–, –S(O) –, –P(O)R–, – P(O)OR–, –P(O)NR2–, –C(O)–, –C(S)–, or

X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR2–, –NR–, –O–, –S–, or –Si(R2)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR2, –P(O)(OR)₂, – P(O)(NR2)OR, –P(O)(NR2)₂, –Si(OH)₂R, –Si(OH)(R)₂, –Si(R)3, or an optionally substituted C1-4 aliphatic; Ring C is a monocyclic or bicyclic ring selected from

each of R² and R^3a is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)3, -S(O)₂R, -S(O)₂N(R)₂, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R2, -OP(O)(OR)₂, - OP(O)(OR)(NR2), -OP(O)(NR2)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R2, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR2), -N(R)P(O)(NR2)₂, or –N(R)S(O)₂R; Ring D is selected from a 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R; R⁵ is hydrogen, C1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L¹ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; m is 0, 1, 2, 3 or 4; n is 0, 1, 2, 3 or 4; p is 0 or 1, wherein when p is 0, the bond connecting Ring C and Ring D is connected to

each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00297] In some embodiments, a compound of formula I-d above is provided as a compound of formula I-dʹ or formula I-dʹʹ:

I-dʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring C, Ring D, L, L¹, R¹, R², R^3a, X¹, X², X³, n, m, and p is as defined above. [00298] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-e:

I-e or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR₂, or an optionally substituted C_1-4 aliphatic; , , ,

, , , , ,

each of R² and R^3a is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R; Ring D is selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or –N(R)S(O)₂R; R⁵ is hydrogen, C_1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, or 2; n is 0, 1, 2, 3 or 4; p is 0 or 1, wherein when p is 0, the bond connecting Ring C and Ring D is connected to

; and each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00299] In some embodiments, a compound of formula I-e above is provided as a compound of formula I-eʹ or formula I-eʹʹ:

I-eʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring C, Ring D, L, R¹, R², R^3a, X¹, n, m, and p is as defined above. [00300] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-f:

I-f or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF₃–, –SO₂–, –S(O) –, –P(O)R–, –

, ,

, , ,

,

, ,

,

each or R² and R^3a is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R2, -OP(O)(OR)₂, - OP(O)(OR)(NR2), -OP(O)(NR2)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R2, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR2), -N(R)P(O)(NR2)₂, or –N(R)S(O)₂R; Ring D is selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R; R⁵ is hydrogen, C_1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L¹ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; m is 0, 1, 2, 3 or 4; n is 0, 1, 2, 3 or 4; p is 0 or 1; and each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00301] In some embodiments, a compound of formula I-f above is provided as a compound of formula I-fʹ or formula I-fʹʹ:

or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring C, Ring D, L, L¹, R¹, R², R^3a, X¹, X², X³, m, n, and p is as defined above. [00302] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-g:

I-g or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR₂, or an optionally substituted C_1-4 aliphatic; Ring C is a monocyclic or bicyclic ring selected from

, ,

, , ,

,

, ,

,

each of R², R^3a, and R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R; Ring D is selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; R⁵ is hydrogen, C1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is 0 or 1; and each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00303] In some embodiments, a compound of formula I-g above is provided as a compound of formula I-gʹ or formula I-gʹʹ:

I-gʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring C, Ring D, L, R¹, R², R^3a, X¹, m, n, and p is as defined above. [00304] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-h:

I-h or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF₃–, –SO₂–, –S(O) –, –P(O)R–, –

X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR₂–, –NR–, –O–, –S–, or –Si(R₂)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, –P(O)(OR)₂, – P(O)(NR₂)OR, –P(O)(NR₂)₂, –Si(OH)₂R, –Si(OH)(R)₂, -Si(R)₃, or an optionally substituted C_1-4 aliphatic; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)3, -S(O)₂R, -S(O)₂N(R)₂, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R2, -OP(O)(OR)₂, - OP(O)(OR)(NR2), -OP(O)(NR2)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R2, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR2), -N(R)P(O)(NR2)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of Ring E, Ring F, and Ring G is independently a fused ring selected from 6-membered aryl, 6- membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, , wherein each of Ring E, Ring F, and Ring G is independently and optionally further substituted with 1-2 oxo groups; L¹ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; and m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16. [00305] Where a point of attachment of

is depicted on Ring E, Ring F, or Ring G, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of

may be on any available carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the ring to which Ring E or Ring G are fused to Ring F. [00306] Where a point of attachment of –(R²)_m is depicted on Ring E, Ring F, or Ring G, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be at any available carbon or nitrogen atom on Ring E, Ring F, or Ring G including the carbon atom to which Ring E or Ring G are fused to Ring F. [00307] Where a point of attachment of

any available carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the carbon atom to which Ring E or Ring G are fused to Ring F. [00308] In some embodiments, a compound of formula I-h above is provided as a compound of formula I-hʹ or formula I-hʹʹ:

I-hʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring E, Ring F, Ring G, L, L¹, R¹, R², X¹, X², X³, and m is as defined above. [00309] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-i:

I-i or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, -Si(R)₃, or an optionally substituted C_1-4 aliphatic; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of Ring E, Ring F, and Ring G is independently a fused ring selected from 6-membered aryl containing 0-3 nitrogens, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, , wherein each of Ring E, Ring F, and Ring G is independently and optionally further substituted with 1-2 oxo groups; and m is 0, 1, 2, 3, or 4. [00310] Where a point of attachment of

may be on any available carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the ring to which Ring E or Ring G are fused to Ring F. [00311] Where a point of attachment of –(R²)_m is depicted on Ring E, Ring F, or Ring G, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be at any available carbon or nitrogen atom on Ring E, Ring F, or Ring G including the carbon atom to which Ring E or Ring G are fused to Ring F. [00312] In some embodiments, a compound of formula I-i above is provided as a compound of formula I-iʹ or formula I-iʹʹ:

I-iʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, L, Ring E, Ring F, Ring G, L, R¹, R², X¹, and m is as defined above. [00313] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-k:

I-k or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF₃–, –SO₂–, –S(O)–, –P(O)R–, –

X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR2–, –NR–, –O–, –S–, or –Si(R2)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, –P(O)(OR)₂, – P(O)(NR2)OR, –P(O)(NR2)₂, –Si(OH)₂R, –Si(OH)(R)₂, -Si(R)3, or an optionally substituted C1-4 aliphatic; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring E is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; Ring H is a fused ring selected from a 7-9 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring E is optionally further substituted with 1-2 oxo groups; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; m is 0, 1, 2, 3, or 4. [00314] Where a point of attachment

is depicted on Ring E or Ring H, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of

may be on any available carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused. [00315] Where a point of attachment of –(R²)_m is depicted on Ring E and Ring H, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)m may be on any available carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused. [00316] Where a point of attachment of

is depicted on Ring E and Ring H, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of

any available carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused. [00317] In some embodiments, a compound of formula I-k above is provided as a compound of formula I-kʹ or formula I-kʹʹ:

or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring E, Ring H, L, L¹, R¹, R², X¹, X², X³, and m is as defined above. [00318] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-l:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, -Si(R)₃, or an optionally substituted C_1-4 aliphatic; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)3, -S(O)₂R, -S(O)₂N(R)₂, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring E is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; Ring H is a ring selected from a 7-9 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring E is optionally further substituted with 1-2 oxo groups; and m is 0, 1, 2, 3, or 4. [00319] Where a point of attachment

may be on any available carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused. [00320] Where a point of attachment of –(R²)_m is depicted on Ring E and Ring H, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be on any available carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused. [00321] Where a point of attachment of

may be on any available carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused. [00322] In some embodiments, a compound of formula I-l above is provided as a compound of formula I-lʹ or formula I-lʹʹ:

or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring E, Ring H, L, R¹, R², X¹, and m is as defined above. [00323] In some embodiments, a compound of formula I-m above is provided as a compound of formula I-m-1:

. I-m-1 or a pharmaceutically acceptable salt thereof, wherein: each of PBM, L, Ring E, X¹, R¹, R², and m is as defined above. [00324] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-n:

I-n or a pharmaceutically acceptable salt thereof, wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF3–, –SO₂–, –S(O) –, –P(O)R–, –

X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR₂–, –NR–, –O–, –S–, or –Si(R₂)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR₂, –P(O)(OR)₂, – P(O)(NR₂)OR, –P(O)(NR₂)₂, –Si(OH)₂R, –Si(OH)(R)₂, –Si(R)₃, or an optionally substituted C_1-4 aliphatic; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, - NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of Ring I and J is independently a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7- membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; Ring K is a fused ring selected from a 6-12 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring H is optionally further substituted with 1-2 oxo groups; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; and m is 0, 1, 2, 3, or 4. [00325] Where a point of attachment of

is depicted on Ring I, Ring J, and Ring K, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of

may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the carbon atom to which Ring I, Ring J, and Ring K are fused. [00326] Where a point of attachment of –(R²)_m is depicted on Ring I, Ring J, and Ring K, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the carbon atom to which Ring I, Ring J, and Ring K are fused. [00327] Where a point of attachment of

may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the carbon atom to which Ring I, Ring J, and Ring K are fused. [00328] In some embodiments, a compound of formula I-n above is provided as a compound of formula I-nʹ or formula I-nʹʹ:

I-nʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring I, Ring J, Ring K, L, L¹, R¹, R², X¹, X², X³, and m is as defined above. [00329] In certain embodiments, the present invention provides a compound of formula I-o:

I-o or a pharmaceutically acceptable salt thereof, wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, -Si(R)3, or an optionally substituted C1-4 aliphatic; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)3, -S(O)₂R, -S(O)₂N(R)₂, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of Ring I and J is independently a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7- membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; Ring K is a fused ring selected from a 6-12 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring H is optionally further substituted with 1-2 oxo groups; and m is 0, 1, 2, 3, or 4. [00330] Where a point of attachment of

may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the carbon atom to which Ring I, Ring J, and Ring K are fused. [00331] Where a point of attachment of –(R²)_m is depicted on Ring I, Ring J, and Ring K, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the carbon atom to which Ring I, Ring J, and Ring K are fused. [00332] Where a point of attachment of

may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the carbon atom to which Ring I, Ring J, and Ring K are fused. [00333] In some embodiments, a compound of formula I-o above is provided as a compound of formula I-oʹ or formula I-oʹʹ:

I-oʹʹ or a pharmaceutically acceptable salt thereof, wherein: each of PBM, Ring I, Ring J, Ring K, L, R¹, R², X¹, and m is as defined above. [00334] In some embodiments, a compound of formula I-o above is provided as a compound of formula I-o-1:

. I-o-1 or a pharmaceutically acceptable salt thereof, wherein: each of PBM, L, Ring I, Ring K, X¹, R¹, R², and m is as defined above. [00335] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-o-2 or I-o-3:

I-o-2

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein: each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -NR₂, - SiR₃, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)NR₂, -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, –N(R)S(O)₂R, - NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)NR₂, -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of Ring E, Ring F, and Ring G is independently a fused ring selected from 6-membered aryl, 6- membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, wherein each of Ring E, Ring F, and Ring G is independently and optionally further substituted with 1-2 oxo groups; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)- , -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S-, -S(O)₂- or -(C)=CH-; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16; and R⁴, R¹⁰, R¹¹, R¹⁵, W¹, W², and X is as defined in WO 2019/099868, the entirety of each of which is herein incorporated by reference. [00336] Where a point of attachment of

may be on any available carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the ring to which Ring E or Ring G are fused to Ring F. _[00337] Where a point of attachment of –(R²)_m is depicted on Ring E, Ring F, or Ring G, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of –(R²)_m may be at any available carbon or nitrogen atom on Ring E, Ring F, or Ring G including the carbon atom to which Ring E or Ring G are fused to Ring F. [00338] Where a point of attachment

depicted on Ring E, Ring F, or Ring G, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment

may be on any available carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the carbon atom to which Ring E or Ring G are fused to Ring F. [00339] As defined above and described herein, X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –C(R)₂–, –C(O)–, –C(S)–, –CH(R)–, –CH(CF3)–, –P(O)(OR)–, –P(O)(R)–, –P(O)(NR2)–, –S(O)–,

[00340] In some embodiments, X¹ is a covalent bond. In some embodiments, X¹ is –CH₂–. In some embodiments, X¹ is –C(R)₂–. In some embodiments, X¹ is –C(O)–. In some embodiments, X¹ is –C(S)–. In some embodiments, X¹ is –CH(R)–. In some embodiments, X¹ is –CH(CF₃)–. In some embodiments, X¹ is –P(O)(OR)–. In some embodiments, X¹ is –P(O)(R)–. In some embodiments, X¹ is –P(O)(NR₂)–. In some embodiments, X¹ is –S(O)–. In some embodiments, X¹ is –S(O)₂–. In some embodiments, X¹ is

[00341] In some embodiments, X¹ is selected from those depicted in Table 2, below. [00342] As defined above and described herein, X² is a carbon atom or silicon atom. [00343] In some embodiments, X² is a carbon atom. In some embodiments, X² is a silicon atom. [00344] In some embodiments, X² is selected from those depicted in Table 2, below. _[00345] As defined above and described herein, X³ is a bivalent moiety selected from –CH₂–, –C(R)₂– , –N(R)–, –CF₂–, –CHF–, –S–, –CH(R)–, –Si(R₂)–, or –O–. [00346] In some embodiments, X³ is –CH₂–. In some embodiments, X¹ is –C(R)₂–. In some embodiments, X³ is –N(R)–. In some embodiments, X³ is –CF₂–. In some embodiments, X³ is –CHF–. In some embodiments, X³ is –S–. In some embodiments, X³ is –CH(R)–. In some embodiments, X³ is – Si(R₂)–. In some embodiments, X³ is –O–. [00347] In some embodiments, X³ is selected from those depicted in Table 2, below. [00348] As defined above and described herein, R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR2, –P(O)(OR)₂, –P(O)(NR2)OR, –P(O)(NR2)₂, –Si(OH)₂R, –Si(OH)(R)₂, –Si(R)3, an optionally substituted C1-4 aliphatic, or R¹ and X¹ or X⁴ are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from nitrogen, oxygen, or sulfur. [00349] In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is deuterium. In some embodiments, R¹ is halogen. In some embodiments, R¹ is –CN. In some embodiments, R¹ is –OR. In some embodiments, R¹ is –SR. In some embodiments, R¹ is –S(O)R. In some embodiments, R¹ is –S(O)₂R. In some embodiments, R¹ is –NR2. In some embodiments, R¹ is –P(O)(OR)₂. In some embodiments, R¹ is –P(O)(NR2)OR. In some embodiments, R¹ is –P(O)(NR2)₂. In some embodiments, R¹ is –Si(OH)₂R. In some embodiments, R¹ is –Si(OH)(R)₂. In some embodiments, R¹ is –Si(R)3. In some embodiments, R¹ is an optionally substituted C1-4 aliphatic. In some embodiments, R¹ and X¹ or X⁴ are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from nitrogen, oxygen, or sulfur. [00350] In some embodiments, R¹ is selected from those depicted in Table 2, below. [00351] As defined above and described herein, each R is independently hydrogen, deuterium, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, or two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, and sulfur. [00352] In some embodiments, R is hydrogen. In some embodiments, R is deuterium. In some embodiments, R is optionally substituted C_1-6 aliphatic. In some embodiments, R is optionally substituted phenyl. In some embodiments, R is optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, R is optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, and sulfur. [00353] In some embodiments, R is selected from those depicted in Table 2, below. [00354] As defined above and described herein, each of R² and R^3a is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, –Si(OH)₂R, –Si(OH)R2, -SR, -NR2, - SiR₃, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR₂, -C(O)N(R)OR, -C(R)₂N(R)C(O)R, - C(R)₂N(R)C(O)NR₂, -OC(O)R, -OC(O)NR₂, -OP(O)R₂, -OP(O)(OR)₂, -OP(O)(OR)NR₂, -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, - N(R)P(O)(OR)NR₂, -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R. [00355] In some embodiments, R² and R^3a is independently hydrogen. In some embodiments, R² and R^3a is independently deuterium. In some embodiments, R² and R^3a is independently –R⁶. In some embodiments, R² and R^3a is independently halogen. In some embodiments, R² and R^3a is independently – CN. In some embodiments, R² and R^3a is independently –NO₂. In some embodiments, R² and R^3a is independently –OR. In some embodiments, R² and R^3a is independently –Si(OH)₂R. In some embodiments, R² and R^3a is independently –Si(OH)R₂. In some embodiments, R² and R^3a is independently –SR. In some embodiments, R² and R^3a is independently -NR₂. In some embodiments, R² and R^3a is independently –SiR₃. In some embodiments, R² and R^3a is independently -S(O)₂R. In some embodiments, R² and R^3a is independently -S(O)₂NR₂. In some embodiments, R² and R^3a is independently –S(O)R. In some embodiments, R² and R^3a is independently –C(O)R. In some embodiments, R² and R^3a is independently – C(O)OR. In some embodiments, R² and R^3a is independently –C(O)NR₂. In some embodiments, R² and R^3a is independently –C(O)N(R)OR. In some embodiments, R² and R^3a is independently - C(R)₂N(R)C(O)R. In some embodiments, R² and R^3a is independently -C(R)₂N(R)C(O)NR₂. In some embodiments, R² and R^3a is independently –OC(O)R. In some embodiments, R² and R^3a is independently –OC(O)NR₂. In some embodiments, R² and R^3a is independently -OP(O)R₂. In some embodiments, R² and R^3a is independently -OP(O)(OR)₂. In some embodiments, R² and R^3a is independently -OP(O)(OR)NR₂. In some embodiments, R² and R^3a is independently -OP(O)(NR₂)₂-. In some embodiments, R² and R^3a is independently –N(R)C(O)OR. In some embodiments, R² and R^3a is independently –N(R)C(O)R. In some embodiments, R² and R^3a is independently –N(R)C(O)NR₂. In some embodiments, R² and R^3a is independently -NP(O)R₂. In some embodiments, R² and R^3a is independently -N(R)P(O)(OR)₂. In some embodiments, R² and R^3a is independently -N(R)P(O)(OR)NR2. In some embodiments, R² and R^3a is independently -N(R)P(O)(NR2)₂. In some embodiments, R² and R^3a is independently –N(R)S(O)₂R. [00356] In some embodiments, R² and R^3a is independently –OH. In some embodiments, R² and R^3a is independently –NH2. In some embodiments, R² and R^3a is independently -CH₂NH2. In some embodiments, R² and R^3a is independently -CH₂NHCOMe. In some embodiments, R² and R^3a is independently – CH₂NHCONHMe. In some embodiments, R² and R^3a is independently -NHCOMe. In some embodiments, R² and R^3a is independently –NHCONHEt. In some embodiments, R² and R^3a is independently -SiMe3. In some embodiments, R² and R^3a is independently –SiMe2OH. In some embodiments, R² and R^3a is independently –SiMe(OH)₂. In some embodiments R² and R^3a is independently

In some embodiments, R² and R^3a is independently Br. In some embodiments, R² and R^3a is independently Cl. In some embodiments, R² and R^3a is independently F. In some embodiments, R² and R^3a is independently Me. In some embodiments, R² and R^3a is independently –NHMe. In some embodiments, R² and R^3a is independently –NMe₂. In some embodiments, R² and R^3a is independently –NHCO₂Et. In some embodiments, R² and R^3a is independently –CN. In some embodiments, R² and R^3a is independently - CH₂Ph. In some embodiments, R² and R^3a is independently -NHCO₂tBu. In some embodiments, R² and R^3a is independently -CO₂tBu. In some embodiments, R² and R^3a is independently -OMe. In some embodiments, R² and R^3a is independently –CF₃. [00357] In some embodiments, R² or R^3a is selected from those depicted in Table 2, below. [00358] As defined above and described herein, R³ is hydrogen, deuterium, halogen, –CN, –NO₂, –OR, –NR₂, –SR, –S(O)₂R, –S(O)₂NR_2, –S(O)R, –C(O)R, –C(O)OR, –C(O)NR₂, –C(O)NR(OR), –OC(O)R, – OC(O)NR₂, –OP(O)(OR)₂, –OP(O)(NR₂)₂, –OP(O)(OR)NR₂, –N(R)C(O)R, – N(R)C(O)OR, -N(R)C(O)NR2, –N(R)S(O)₂R, –N(R)S(O)₂NR2, –N(R)P(O)(OR)₂, –N(R)P(O)(OR)NR2, – P(O)(OR)₂, –P(O)(NR2)OR, –P(O)(NR2)₂, –Si(OH)₂R, –Si(OH)(R)₂, or –Si(R)3. [00359] In some embodiments, R³ is hydrogen. In some embodiments, R³ is deuterium. In some embodiments, R³ is halogen. In some embodiments, R³ is –CN. In some embodiments, R³ is –NO₂. In some embodiments, R³ is –OR. In some embodiments, R³ is –NR2. In some embodiments, R³ is –SR. In some embodiments, R³ is –S(O)₂R. In some embodiments, R³ is –S(O)₂NR2. In some embodiments, R³ is – S(O)R. In some embodiments, R³ is –C(O)R. In some embodiments, R³ is –C(O)OR. In some embodiments, R³ is –C(O)NR₂. In some embodiments, R³ is –C(O)NR(OR). In some embodiments, R³ is –OC(O)R. In some embodiments, R³ is –OC(O)NR₂. In some embodiments, R³ is –OP(O)(OR)₂. In some embodiments, R³ is –OP(O)(NR₂)₂. In some embodiments, R³ is –OP(O)(OR)NR₂. In some embodiments, R³ is – N(R)C(O)R. In some embodiments, R³ is –N(R)C(O)OR. In some embodiments, R³ is –N(R)C(O)NR₂. In some embodiments, R³ is –N(R)S(O)₂R. In some embodiments, R³ is –N(R)S(O)₂NR₂. In some embodiments, R³ is –N(R)P(O)(OR)₂. In some embodiments, R³ is –N(R)P(O)(OR)NR2. In some embodiments, R³ is –P(O)(OR)₂. In some embodiments, R³ is –P(O)(NR2)OR. In some embodiments, R³ is –P(O)(NR2)₂. In some embodiments, R³ is –Si(OH)₂R. In some embodiments, R³ is –Si(OH)(R)₂. In some embodiments, R³ is –Si(R)3. [00360] In some embodiments, R³ is methyl. In some embodiments, R³ is –OCH3. In some embodiments, R³ is chloro. [00361] In some embodiments, R³ is selected from those depicted in Table 2, below. [00362] As defined above and described herein, each R⁴ is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -NR2, –S(O)₂R, –S(O)₂NR2, –S(O)R, –C(O)R, –C(O)OR, –C(O)NR2, – C(O)N(R)OR, –OC(O)R, –OC(O)NR2, –N(R)C(O)OR, –N(R)C(O)R, –N(R)C(O)NR2, –N(R)S(O)₂R, – P(O)(OR)₂, –P(O)(NR₂)OR, or –P(O)(NR₂)₂. _[00363] In some embodiments, R⁴ is hydrogen. In some embodiments, R⁴ is –R⁶. In some embodiments, R⁴ is halogen. In some embodiments, R⁴ is –CN. In some embodiments, R⁴ is –NO₂. In some embodiments, R⁴ is –OR. In some embodiments, R⁴ is –SR. In some embodiments, R⁴ is –NR₂. In some embodiments, R⁴ is –S(O)₂R. In some embodiments, R⁴ is –S(O)₂NR₂. In some embodiments, R⁴ is – S(O)R. In some embodiments, R⁴ is –C(O)R. In some embodiments, R⁴ is –C(O)OR. In some embodiments, R⁴ is –C(O)NR₂. In some embodiments, R⁴ is –C(O)N(R)OR. In some embodiments, R⁴ is –OC(O)R. In some embodiments, R⁴ is –OC(O)NR₂. In some embodiments, R⁴ is –N(R)C(O)OR. In some embodiments, R⁴ is –N(R)C(O)R. In some embodiments, R⁴ is –N(R)C(O)NR₂. In some embodiments, R⁴ is –N(R)S(O)₂R. In some embodiments, R⁴ is –P(O)(OR)₂. In some embodiments, R⁴ is –P(O)(NR₂)OR. In some embodiments, R⁴ is –P(O)(NR₂)₂. [00364] In some embodiments, R⁴ is methyl. In some embodiments, R⁴ is ethyl. In some embodiments, R⁴ is cyclopropyl. [00365] In some embodiments, R⁴ is selected from those depicted in Table 2, below. [00366] As defined above and described herein, R⁵ is hydrogen, deuterium, an optionally substitute C1- 4 aliphatic, or –CN. [00367] In some embodiments, R⁵ is hydrogen. In some embodiments, R⁵ is deuterium. In some embodiments, R⁵ is an optionally substituted C1-4 aliphatic. In some embodiments, R⁵ is –CN. [00368] In some embodiments, R⁵ is selected from those depicted in Table 2, below. [00369] As defined above and described herein, each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. [00370] In some embodiments, R⁶ is an optionally substituted C_1-6 aliphatic. In some embodiments, R⁶ is an optionally substituted phenyl. In some embodiments, R⁶ is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, R⁶ is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. [00371] In some embodiments, R⁶ is selected from those depicted in Table 2, below. [00372] As defined above and described herein, Ring A is a bi- or tricyclic ring selected from , , ,

, , , ,

o

r . [00373] In some embodiments, Ring A is

. In some embodiments, Ring A is In some embodiments, Ring A is

. In some embodiments, Ring A is In some embodiments, Ring A is

In some embodiments, Ring A is In some embodiments, Ring A is

In some embodiments, Ring A is In some embodiments, Ring A is

In some embodiments, Ring A is In some embodiments, Ring A is

In some embodiments, Ring A is

some embodiments, Ring A is

. , . In some embodiments, Ring A is

some embodiments, Ring A is e e

[00374] In some embodiments, Ring

In some embodiments, Ring A is In some embodiments, Ring

some embodiments, Ring A is

. In some embodiments, Ring

some embodiments, Ring A is

. , . In some embodiments, Ring A is me embodiments, Ring A i

some embodiments, Ring

A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring some embodiments, Ring

some embodiments, Ring

some embodiments, Ring

[00375] In some embodiments, Ring A is selected from those depicted in Table 2, below. [00376] As defined above and described herein, Ring B is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; [00377] In some embodiments, Ring B is a fused 6-membered aryl. In some embodiments, Ring B is a fused 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Ring B is a fused 5 to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, Ring B is fused 5 to 7-membered saturated or partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring B is fused 5-membered heteroaryl with 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur.

. , . [00379] In some embodiments, each Ring some embodiments, each Ring B is me embodiments, each

Ring some embodiments, each Ring B i

some embodiments, Ring

. , . ,

[ some embodiments, Ring

In some embodiments, Ring B is

. In some embodiments, Ring

In some embodiments, Ring B is In some embodiments, Ring

In some embodiments, Ring B is

. In some embodiments, Ring

[

. In some embodiments, Ring B is . In some embodiments, Ring B is

, , , ,

[00384] In some embodiments, Ring B is selected from those depicted in Table 2, below. [00385] As defined above and described herein, Ring C is a monocyclic or bicyclic ring selected from , , , ,

[00386] In some embodiments, Ring

In some embodiments, Ring C is

. In some embodiments, Ring C is . In some embodiments, Ring C is

. In some embodiments, Ring C is . In some embodiments, Ring C is

. , . ,

. , . ,

. , . ,

some embodiments, Ring C is

. In some embodiments, Ring C is

. In some embodiments, Ring C is

some embodiments, Ring C is

. , . [00388] In some embodiments, Ring C is a monocyclic or bicyclic ring selected from

, , , ,

,

, , ,

,

[

[00390] In some embodiments, Ring C is selected from

, ,

[00391] In some embodiments, Ring C is selected from those depicted in Table 2, below. [00392] As defined above and described herein, Ring D is a ring selected from 6-membered aryl, 6- membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; [00393] In some embodiments, Ring D is a 6-membered aryl. In some embodiments, Ring D is a 6- membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Ring D is a 5 to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, Ring D is 5 to 7-membered saturated or partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring D is 5-membered heteroaryl with 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. [00394] In some embodiments, Ring D is selected from those depicted in Table 2, below. [00395] As defined above and described herein, each of Ring E, Ring F, and Ring G is independently a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1- 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, wherein each of Ring E, Ring F, and Ring G is independently and optionally further substituted with 1-2 oxo groups. [00396] In some embodiments, each Ring E, Ring F, and Ring G is independently a 6-membered aryl. In some embodiments, each Ring E, Ring F, and Ring G is independently a 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, each Ring E, Ring F, and Ring G is independently a 5 to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, each Ring E, Ring F, and Ring G is independently a 5 to 7-membered saturated or partially unsaturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, each Ring E, Ring F, and Ring G is independently a 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. In some embodiments, each of Ring E, Ring F, and Ring G is independently and optionally further substituted with 1-2 oxo groups. [00397] In some embodiments, Ring

some embodiments, Ring F is

In some embodiments, Ring

some embodiments, Ring

. In some embodiments, Ring

In some embodiments, Ring F is

some embodiments,

In some embodiments, Ring F is

. In some embodiments, Ring F is

. , . In some embodiments, Ring F is

. In some embodiments, Ring F is

In some embodiments, Ring F is

. In some embodiments, Ring F is [

embodiments, Ring F is

. In some embodiments, Ring F is e

In some embodiments, Ring F is

. In some embodiments, Ring F is e

In some

. [00399] In some embodiments, each Ring E and Ring G is independently

. In some embodiments, each Ring E and Ring G is independently

. In some embodiments, each Ring E and Ring G is i

. [00400] In some embodiments, Ring E and Ring G is independently is

. In some embodiments, Ring E and Ring G is independently

. In some embodiments, Ring E and Ring G is independently In some embodiments, Ring E and Ring G is independently

. In some embodiments, Ring E and Ring G is independently

.

[00401] In some embodiments, Ring E and Ring G is independently . In some embodiments, Ring E and Ring G is independently

. In some embodiments, Ring E and S (R²)_m N Ring G is independently H . In some embodiments, Ring E and Ring G is independently

. In some embodiments, Ring E and Ring G is independently

. [00402] In some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

some embodiment, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring G is

. In some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E,

some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E,

[00403] In some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring G is

In some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E, Ring F, and

In some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

some embodiments, Ring E, Ring F, and Ring

In some embodiments, Ring E, Ring F, and Ring

[00404] In some embodiments, Ring E, Ring F, and Ring G is selected from those depicted in Table 2, below. [00405] As defined above and described herein, Ring H is a ring selected from a 7-9 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring E is optionally further substituted with 1-2 oxo groups. [00406] In some embodiments, Ring H is a ring selected from a 7-9 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring H is optionally further substituted with 1-2 oxo groups. [00407] In some embodiments, Ring

some embodiments, Ring H is . In some embodiments, Ring

In some e is

. In some embodiments, Ring H is

. In some embodiments, Ring

. In some embodiments, Ring H is

. In some embodiments, Ring H is

. some embodiments, Ring H is

. In some embodiments, Ring H is

In some embodiments, Ring H is

. In some embodiments, Ring H is

In some embodiments, Ring H is

. In some embodiments, Ring H is

In some embodiments, Ring H is . In some embodiments, Ring H is

[00408] In some embodiments, Ring E and Ring

[00409] In some embodiments, Ring E and Ring H is selected from those depicted in Table 2, below. [00410] As defined above and described herein, each of Ring I and Ring J is independently a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7- membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur [00411] In some embodiments, each of Ring I and Ring J is independently a 6-membered aryl. In some embodiments, each of Ring I and Ring J is independently a 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, each of Ring I and Ring J is independently a 5 to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, each of Ring I and Ring J is independently a 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, each of Ring I and Ring J is independently a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur. [00412] In some embodiments, each Ring I and Ring J is independently

. In some embodiments, each Ring I and Ring J is independently

. In some embodiments, each Ring I and Ring J is independently

. In some embodiments, each Ring I and Ring J is independently

. In some embodiments, Ring I and Ring J is independently

. [00413] In some embodiments, Ring I and Ring J is independently is

some embodiments, Ring I and Ring J is independently

. In some embodiments, Ring I and Ring J is independently

. [00414] As defined above and described herein, Ring K is a fused ring selected from a 6-12 membered saturated or partially unsaturated carbocyclyl or heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring H is optionally further substituted with 1-2 oxo groups. [00415] In some embodiments, Ring K is a fused ring selected from a 6-12 membered saturated or partially unsaturated carbocyclyl. In some embodiments, Ring K is a 6-12 membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring K is optionally further substituted with 1-2 oxo groups. [00416] In some embodiments, Ring

some embodiments, Ring K is

In some embodiments, Ring K is

. In some embodiments, Ring K is

In some embodiments, Ring K i

In some embodiments, Ring K is

some embodiments, Ring K i

In some embodiments, Ring K is

some embodiments, Ring K i

In some embodiments, Ring K is

[00417] In some embodiments, Ring I, Ring J, and Ring

[00418] In some embodiments, Ring I, Ring J, and Ring K is selected from those depicted in Table 2, below. [00419] As defined above and described here, L¹ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)-, -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; [00420] In some embodiments, L¹ is a covalent bond. In some embodiments, L¹ is a C_1-3 aliphatic. In some embodiments, L¹ is –CH₂–. In some embodiments, L¹ is –C(D)(H)-. In some embodiments, L¹ is - C(D)₂–. In some embodiments, L¹ is –CH₂CH₂–. In some embodiments, L¹ is –NR–. In some embodiments, L¹ is –CH₂NR–. In some embodiments, L¹ is or –O–. In some embodiments, L¹ is –CH₂O– . In some embodiments, L¹ is –S–. In some embodiments, L¹ is -OC(O)-. In some embodiments, L¹ is - C(O)O-. In some embodiments, L¹ is -C(O)-. In some embodiments, L¹ is -S(O)-. In some embodiments, L¹ is -S(O)₂-,. In some embodiments, L¹ is -NRS(O)₂-. In some embodiments, L¹ is -S(O)₂NR-. In some embodiments, L¹ is -NRC(O)-. In some embodiments, L¹ is -C(O)NR-. [00421] In some embodiments, Ring L¹ is selected from those depicted in Table 2, below. [00422] As defined above and described herein, is a single or double bond. [00423] In some embodiments, is a single bond. In some embodiments, is a double bond. [00424] In some embodiments, is selected from those depicted in Table 2, below. [00425] As defined above and described herein, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16. [00426] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 7. In some embodiments, m is 8. In some embodiments, m is 9. In some embodiments, m is 10. In some embodiments, m is 11. In some embodiments, m is 12. In some embodiments, m is 13. In some embodiments, m is 14. In some embodiments, m is 15. In some embodiments, m is 16. [00427] In some embodiments, m is selected from those depicted in Table 2, below. [00428] As defined above and described herein, n is 0, 1, 2, 3 or 4. [00429] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. [00430] In some embodiments, n is selected from those depicted in Table 2, below. [00431] As defined above and described herein, p is 0 or 1. [00432] In some embodiments, p is 0. In some embodiments, p is 1. [00433] In some embodiments, p is selected from those depicted in Table 2, below. [

embodiments, LBM is

. In some embodiments, LBM is e [

e [ i e

embodiments, LBM is . In some embodiments, LBM is

. [00437] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-p-1, I- p-2, or I-p-3 respectively:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described herein, and wherein each of the variables R¹, R², R⁴, R⁵, R¹⁰, R¹¹, R¹⁴, R¹⁷, W¹, W², X, , and n is as defined in WO 2017/197051 which is herein incorporated by reference in its entirety and wherein

is attached to R¹, the ring formed by combining R¹ and R², or R¹⁷ at the site of attachment of R¹² as defined in WO 2017/197051 such that

takes the place of the R¹² substituent. [00438] In some embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-p-4, I-p-5, I-p-6, or I-p-7, respectively:

I-p-7 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described herein, and wherein each of the variables R¹, R⁴, R¹⁰, R¹¹, R¹⁴, R¹⁶, W¹, W², X, , and n is as defined in WO 2018/237026, the entirety of each of which is herein incorporated by reference, and wherein s

[00439] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is a MDM2 (i.e. human double minute 2 or HDM2) E3 ligase binding moiety thereby forming a compound of formula I-q-1, I-q-2, I-q-3, I-q-4, I-q-5, I-q-6, I-q-7, I-q-8, I-q-9, I-q-10, I-q-11, I-q-12, I- q-13, I-q-14, I-q-15, I-q-16, I-q-17, or I-q-18 respectively:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, R₂₅, R₂₆, R₂₇, R₂₈, R_1’, R_2’, R_3’, R_4’, R_5’, R_6’, R_7’, R_8’, R_9’, R_10’, R_11’, R_12’, R_1’’, A, A’, A’’, X, Y, and Z is as defined and described in WO 2017/011371 and US 2017/008904, the entirety of each of which is herein incorporated by reference. [00440] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is a MDM2 (i.e. human double minute 2 or HDM2) E3 ligase binding moiety thereby forming a compound of formula I-q-19, I-q-20, or I-q-21 respectively:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R^12c, R^12d, R¹³, R¹⁷, R^18b, R^18c, R^18d, A⁵, A⁶, A⁷, Q¹, and Ar is as defined and described in WO 2017/176957 and US2019/127387, the entirety of each of which is herein incorporated by reference. [00441] In some embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-r-1 or I-r-3, respectively:

I-r-3 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described herein, and wherein each of the variables R¹, R¹⁴, and R¹⁶ is as defined in WO 2018/237026, the entirety of each of which is herein incorporated by reference, and wherein

is attached to R¹ or R¹⁶ at the site of attachment of R¹² as defined in WO 2018/237026, such that

takes the place of the R¹² substituent. [00442] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-s:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables A, B, C, W, X, Y, and Z is as described and defined in US 5,721,246, the entirety of each of which is herein incorporated by reference. [00443] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-t:

I-t or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, and n is as described and defined in WO 2019/043214, the entirety of each of which is herein incorporated by reference. [00444] In some embodiments, LBM is a IAP E3 Ubiquitin ligase binding moiety recited in Varfolomeev, E. et al., IAP Antagonists Induce Autoubiquitination of c-IAPs, NF-κB activation, and TNFα- Dependent Apoptosis, Cell, 2007, 131(4): 669-81, such as, for example:

MV1

wherein

is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom. [00445] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an IAP E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-u-1, I-u-2, I- u-3, or I-u-4 respectively:

I-u-2

I-u-4 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R¹, R², R³, R⁴, R⁵, R⁶, and R⁷, is as defined and described in WO 2017/011590 and US 2007/037004, the entirety of each of which is herein incorporated by reference. [00446] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an IAP binding moiety thereby forming a compound of formula I-v:

I-v or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables W, Y, Z, R¹, R², R³, R⁴, and R⁵ is as described and defined in WO 2014/044622, US 2015/0225449. WO 2015/071393, and US 2016/0272596, the entirety of each of which is herein incorporated by reference. [00447] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a MDM2 binding moiety thereby forming a compound of formula I-w:

I-w or a pharmaceutically acceptable salt thereof, as described and defined in Hines, J. et al., Cancer Res. (DOI: 10.1158/0008-5472.CAN-18-2918), the entirety of each of which is herein incorporated by reference. [00448] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a DCAF16 binding moiety thereby forming a compound of formula I-x:

I-x or a pharmaceutically acceptable salt thereof, as described and defined in Zhang, X. et al., bioRxiv (doi: https://doi.org/10.1101/443804), the entirety of each of which is herein incorporated by reference. [00449] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a RNF114 binding moiety thereby forming a compound of formula I-y:

I-y or a pharmaceutically acceptable salt thereof, as described and defined in Spradin, J.N. et al., bioRxiv (doi: https://doi.org/10.1101/436998), the entirety of each of which is herein incorporated by reference. [00450] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a RNF4 binding moiety thereby forming a compound of formula I-z:

I-z or a pharmaceutically acceptable salt thereof, as described and defined in Ward, C.C., et al., bioRxiv (doi: https://doi.org/10.1101/439125), the entirety of each of which is herein incorporated by reference. [00451] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a VHL binding moiety thereby forming a compound of formula I-aa-1 or I-aa-2:

I-aa-2 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R¹, R², R³, X, and Y is as defined and described in WO 2019/084026, the entirety of each of which is herein incorporated by reference. [00452] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a VHL binding moiety thereby forming a compound of formula I-aa-3 or I-aa-3:

I-aa-4 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R¹, R³, and Y is as defined and described in WO 2019/084030, the entirety of each of which is herein incorporated by reference. [00453] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is a VHL E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-aa-5, I-aa-6, I-aa-7, I-aa-8, or I-aa-9 respectively:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R^1’, R^2’, R^3’, X, and X’ is as defined and described in WO 2013/106643 and US 2014/0356322, the entirety of each of which is herein incorporated by reference. [00454] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a VHL E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-aa-10, I-aa- 11, I-aa-12, I-aa-13, I-aa-14 or I-aa-15 respectively:

I-aa-12 I-aa-13

I-aa-14 I-aa-15 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R^1’, R^2’, R^3’, R5, R6, R7, R9, R10, R11, R14, R15, R16, R₁₇, R₂₃, R₂₅, E, G, M, X, X’, Y, Z₁, Z₂, Z₃, Z₄, and o is as defined and described in WO 2016/149668 and US 2016/0272639 the entirety of each of which is herein incorporated by reference. [00455] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a VHL E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-aa-16, I-aa- 17, or I-aa-18 respectively: I-aa-16

I-aa-17

I-aa-18 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R^p, R9, R10, R11, R14a, R14b, R15, R16, W³, W⁴, W⁵, X¹, X², and o is as defined and described in WO 2016/118666 and US 2016/0214972, the entirety of each of which is herein incorporated by reference. [00456] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-bb-1, I- bb-2, I-bb-3, or I-bb-4:

I-bb-3

I-bb-4 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described herein, and wherein each of the variables R⁴, R¹⁰, R¹¹, R¹⁵, R¹⁶, R¹⁷, W¹, W², and X is as defined in WO 2019/099868 which is herein incorporated by reference in its entirety, and wherein

is attached to R¹⁷ or R¹⁶ at the site of attachment of R¹² as defined in WO 2018/237026, such that

takes the place of the R¹² substituent.

In some embodiments,

In some embodiments, LBM is

In some embodiments,

some embodiments, LBM is

some embodiments, LBM is

. In some embodiments, LBM is

In some embodiments,

In some embodiments, LBM is

[00458] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-cc:

I-cc or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, wherein: each X¹ is independently -

X² and X³ are independently -

Z¹ and Z² are independently a carbon atom or a nitrogen atom; Ring A is a fused ring selected from benzo, a 4-6 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -S-, -C(O)-, -C(S)-, -CR₂-, -CRF-, -CF₂-, -NR-, or -S(O)₂-; each R¹ is independently selected from hydrogen, deuterium, R⁴, halogen, -CN, -NO₂, -OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -CF₂R, -CR₂F, -CF₃, -CR₂(OR), - CR₂(NR₂), -C(O)R, -C(O)OR, -C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -C(S)NR₂, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, -N(R)S(O)₂R, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)NR2, -OP(O)(NR2)₂, -Si(OR)R2, and -SiR3; or two R¹ groups are optionally taken together to form an optionally substituted 5-8 membered partially unsaturated or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R is independently selected from hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same carbon or nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the carbon or nitrogen, independently selected from nitrogen, oxygen, and sulfur;

Ring B is phenyl, a 4-10 membered saturated or partially unsaturated mono- or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Ring B is further optionally substituted with 1-2 oxo groups; each R³ is independently selected from hydrogen, deuterium, R⁴, halogen, -CN, -NO₂, -OR, - SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -CF2R, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, - C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, - N(R)S(O)₂R, -OP(O)R2, -OP(O)(OR)₂, -OP(O)(OR)NR2, -OP(O)(NR2)₂, and -SiR3; each R⁴ is independently selected from an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; is a single or double bond; m is 0, 1, 2, 3 or 4; n is 0, 1, 2, 3 or 4; and o is 0, 1, or 2. [00459] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-dd:

I-dd or a pharmaceutically acceptable salt thereof, wherein: X¹ and X⁴ are independently a covalent bond, -CR2-, -O-,

; X² and X³ are independently -

Ring C is a spiro-fused ring selected from a 4-10 membered saturated or partially unsaturated mono- or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Ring C is optionally further substituted with 1-2 oxo groups; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -S-, -C(O)-, -C(S)-, -CR₂-, -CRF-, -CF₂-, -NR-, or -S(O)₂-; each R¹ is independently selected from hydrogen, deuterium, R⁴, halogen, -CN, -NO₂, -OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -CF₂R, -CF₃, -CR₂(OR), -CR₂(NR₂), -C(O)R, -C(O)OR, - C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -C(S)NR₂, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, -N(R)S(O)₂R, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)NR₂, -OP(O)(NR₂)₂, -Si(OR)R₂, and -SiR₃; or two R¹ groups are optionally taken together to form an optionally substituted 5-8 membered partially unsaturated or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R is independently selected from hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same carbon or nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the carbon or nitrogen, independently selected from nitrogen, oxygen, and sulfur; R² is selected from or hydrogen; Ring B is phenyl, a 4-10 membered saturated or partially unsaturated mono- or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Ring B is further optionally substituted with 1-2 oxo groups; each R³ is independently selected from hydrogen, deuterium, R⁴, halogen, -CN, -NO₂, -OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -CF₂R, -CF₃, -CR₂(OR), -CR₂(NR₂), -C(O)R, -C(O)OR, - C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, - N(R)S(O)₂R, -OP(O)R2, -OP(O)(OR)₂, -OP(O)(OR)NR2, -OP(O)(NR2)₂, and -SiR3; each R⁴ is independently selected from an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3 or 4; and n is 0, 1, 2, 3 or 4. _[00460] As defined above and described herein X¹ is a covalent bond,

,

[00461] In some embodiments, X¹ is a covalent bond. In some embodiments, X¹ is -CH₂-. In some embodiments, X¹ is -O-. In some embodiments, X¹ is -NR-. In some embodiments, X¹ is -CF₂-. In some embodiments, X¹ is

. In some embodiments, X¹ is -C(O)-. In some embodiments, X¹ is -C(S)-. In some embodiments,

[00462] In certain embodiments, X¹ is selected from those shown in the compounds of Table 2. [00463] As defined above and described herein, X² and X³ are independently -CH₂-, -C(O)-, -C(S)-, or

. [00464] In some embodiments, X² and X³ are independently -CH₂-. In some embodiments, X² and X³ are independently -C(O)-. In some embodiments, X² and X³ are independently -C(S)-. In some embodiments, X² and X³ are independently

. [00465] In certain embodiments, X² and X³ are independently selected from those shown in the compounds of Table 2. [00466] As defined above and described herein, X⁴ is a covalent bond, -CH₂-, -CR₂-, -O-, -NR-, -CF₂-,

[00467] In some embodiments, X⁴ is a covalent bond. In some embodiments, X⁴ is -CH₂-. In some embodiments, X⁴ is -CR2-. In some embodiments, X⁴ is -O-. In some embodiments, X⁴ is -NR-. In some embodiments, X⁴ is -CF₂-. In some embodiments, X⁴ is

. In some embodiments, X⁴ is -C(O)-. In some embodiments, X⁴ is -C(S)-. In some embodiments, X⁴ is

. [00468] In certain embodiments, X⁴ is selected from those shown in the compounds of Table 2. [00469] As define above and described herein, Z¹ and Z² are independently a carbon atom or a nitrogen atom. [00470] In some embodiments, Z¹ and Z² are independently a carbon atom. In some embodiments, Z¹ and Z² are independently a carbon atom. [00471] In certain embodiments, Z¹ and Z² are independently selected from those shown in the compounds of Table 2. [00472] As defined above and described herein, Ring A is fused ring selected from benzo or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [00473] In some embodiments, Ring A is benzo. In some embodiments, Ring A is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [00474] In some embodiments, Ring

In some embodiments, Ring A is In some embodiments, Ring

some embodiments, Ring A is

. In some embodiments, Ring

[00475] In certain embodiments, Ring A is selected from those shown in the compounds of Table 2. [00476] In some embodiments, Ring C is a spiro-fused ring selected from a 4-10 membered saturated or partially unsaturated mono- or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring C is optionally further substituted with 1-2 oxo groups. [00477] In some embodiments, Ring

some embodiments, Ring C is

. , . In some embodiments, Ring C is

. In some embodiments, Ring C is

. In some embodiments, Ring C is . In some e

. [00478] In certain embodiments, Ring C is selected from those shown in the compounds of Table 2. _[00479] As defined above and described herein, L¹ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -S-, -C(O)-, -C(S)-, -CR₂-, -CRF-, -CF₂-, -NR-, or -S(O)₂- . [00480] In some embodiments, L¹ is a covalent bond. In some embodiments, L¹ is a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -S-, -C(O)-, -C(S)-, -CR₂-, -CRF-, -CF₂-, -NR-, or - S(O)₂-. [00481] In some embodiments, L¹ is -C(O)-. [00482] In certain embodiments, L¹ is selected from those shown in the compounds of Table 2. [00483] As defined above and described herein, each R¹ is independently selected from hydrogen, deuterium, R⁴, halogen, -CN, -NO₂, -OR, -SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -CF2R, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -C(S)NR2, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)₂R, -OP(O)R2, -OP(O)(OR)₂, -OP(O)(OR)NR2, - OP(O)(NR2)₂, -Si(OR)R2, and -SiR3, or two R¹ groups are optionally taken together to form an optionally substituted 5-8 membered partially unsaturated or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [00484] In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is deuterium. In some embodiments, R¹ is R⁴. In some embodiments, R¹ is halogen. In some embodiments, R¹ is –CN. In some embodiments, R¹ is -NO₂. In some embodiments, R¹ is –OR. In some embodiments, R¹ is –SR. In some embodiments, R¹ is -NR2. In some embodiments, R¹ is -S(O)₂R. In some embodiments, R¹ is -S(O)₂NR2. In some embodiments, R¹ is -S(O)R. In some embodiments, R¹ is -CF₂R. In some embodiments, R¹ is - CF₃. In some embodiments, R¹ is -CR₂(OR). In some embodiments, R¹ is -CR₂(NR₂). In some embodiments, R¹ is -C(O)R. In some embodiments, R¹ is -C(O)OR. In some embodiments, R¹ is - C(O)NR₂. In some embodiments, R¹ is -C(O)N(R)OR. In some embodiments, R¹ is -OC(O)R. In some embodiments, R¹ is -OC(O)NR₂. In some embodiments, R¹ is -C(S)NR₂. In some embodiments, R¹ is - N(R)C(O)OR. In some embodiments, R¹ is -N(R)C(O)R. In some embodiments, R¹ is -N(R)C(O)NR₂. In some embodiments, R¹ is -N(R)S(O)₂R. In some embodiments, R¹ is -OP(O)R₂. In some embodiments, R¹ is -OP(O)(OR)₂,. In some embodiments, R¹ is -OP(O)(OR)NR₂. In some embodiments, R¹ is - OP(O)(NR₂)₂. In some embodiments, R¹ is -Si(OR)R₂. In some embodiments, R¹ is -SiR₃. In some embodiments, two R¹ groups are optionally taken together to form an optionally substituted 5-8 membered partially unsaturated or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [00485] In some embodiments, R¹ is fluoro. In some embodiments, R¹ is bromo. In some embodiments, R¹ is methyl. In some embodiments, R¹ is -OH. In some embodiments, R¹ is -NH2. In some embodiments, R¹ is -NHCH3. In some embodiments, R¹ is -N(CH3)₂. In some embodiments, R¹ is -NHCH(CH3)₂. In some embodiments, R¹ is -NHSO₂CH3. In some embodiments, R¹ is -CH₂OH. In some embodiments, R¹ is -CH₂NH2. In some embodiments, R¹ is -C(O)NH2. In some embodiments, R¹ is -C(O)NHCH3. In some embodiments, R¹ is

. In some embodiments, R¹

In some embodiments, R¹ is . In some embodiments, R¹ is . In some embodiments, R¹ is

. In some embodiments, R¹ is

. , . , . [00486] In certain embodiments, each R¹ is independently selected from those shown in the compounds of Table 2. [00487] As defined above and described here, each R is independently selected from hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or two R groups on the same carbon or nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the carbon or nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00488] In some embodiments, R is hydrogen. In some embodiments, R is an optionally substituted C_1- 6 aliphatic. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, two R groups on the same carbon or nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the carbon or nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00489] As defined above and described herein, R² is selected from

or hydrogen. [00490] In some embodiment R² is . In some embodiments, R² is hydrogen. [00491] In certain embodiments, R² is selected from those shown in the compounds of Table 2. [00492] As defined above and described herein, Ring B is phenyl, a 4-10 membered saturated or partially unsaturated mono- or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Ring B is further optionally substituted with 1-2 oxo groups. [00493] In some embodiments, Ring B is phenyl. In some embodiments, Ring B is a 4-10 membered saturated or partially unsaturated mono- or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur In some embodiments, Ring B is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring B is further optionally substituted with 1-2 oxo groups. [00494] In some embodiments, Ring

In some embodiments, Ring B is

. In some embodiments, Ring B is

. In some embodiments Ring B is

some embodiments Ring

some embodiments

embodiments Ring B is

. In some embodiments Ring B is

[00495] In certain embodiments, Ring B is selected from those shown in the compounds of Table 2. [00496] As defined above and described herein, each R³ is independently selected from hydrogen, deuterium, R⁴, halogen, -CN, -NO₂, -OR, -SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -CF2R, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, - N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)₂R, -OP(O)R2, -OP(O)(OR)₂, -OP(O)(OR)NR2, - OP(O)(NR2)₂, and -SiR3. [00497] In some embodiments, R³ is hydrogen. In some embodiments, R³ is deuterium. In some embodiments, R³ is R⁴. In some embodiments, R³ is halogen. In some embodiments, R³ is –CN. In some embodiments, R³ is -NO₂. In some embodiments, R³ is –OR. In some embodiments, R³ is –SR. In some embodiments, R³ is -NR₂. In some embodiments, R³ is -S(O)₂R. In some embodiments, R³ is -S(O)₂NR₂. In some embodiments, R³ is -S(O)R. In some embodiments, R³ is -CF₂R. In some embodiments, R³ is - CF₃. In some embodiments, R³ is -CR₂(OR) . In some embodiments, R³ is -CR₂(NR₂) . In some embodiments, R³ is -C(O)R. In some embodiments, R³ is -C(O)OR. In some embodiments, R³ is - C(O)NR₂. In some embodiments, R³ is -C(O)N(R)OR. In some embodiments, R³ is -OC(O)R. In some embodiments, R³ is -OC(O)NR₂. In some embodiments, R³ is -N(R)C(O)OR. In some embodiments, R³ is -N(R)C(O)R. In some embodiments, R³ is -N(R)C(O)NR₂. In some embodiments, R³ is -N(R)S(O)₂R. In some embodiments, R³ is -OP(O)R₂. In some embodiments, R³ is -OP(O)(OR)₂. In some embodiments, R³ is -OP(O)(OR)NR₂. In some embodiments, R³ is -OP(O)(NR₂)₂. In some embodiments, R³ is -SiR₃. [00498] In certain embodiments, R³ is selected from those shown in the compounds of Table 2. [00499] As defined above and described herein, each R⁴ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [00500] In some embodiments, R⁴ is an optionally substituted C_1-6 aliphatic. In some embodiments, R⁴ is an optionally substituted phenyl. In some embodiments, R⁴ is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R⁴ is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [00501] In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. , . In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. In some embodiments,

some embodiments, R . In some embodiments,

. In some embodiments, R⁴ is In some embodiments,

. In some embodiments, R⁴ is

. some embodiments,

. In some embodiments, R⁴ is

In some embodiments, R⁴ is

. , . In some embodiments,

some embodiments, R⁴ is

. In some embodiments, R⁴ is

. In some embodiments,

is . In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. In some embodiments, R⁴ is . In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. , . In some embodiments, R⁴ is

. , . In some embodiments, R⁴ is . In some embodiments, R⁴ is

. In some embodiments, R⁴ is

. [00502] In certain embodiments, R⁴ is selected from those shown in the compounds of Table 2. [00503] As defined above and described herein, is a single or double bond. [00504] In some embodiments, is a single bond. In some embodiments, is a double bond. [00505] In certain embodiments, is selected from those shown in the compounds of Table 2. [00506] As defined above and described herein, m is 0, 1, 2, 3 or 4. [00507] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. [00508] In certain embodiments, m is selected from those shown in the compounds of Table 2. [00509] As defined above and described herein, n is 0, 1, 2, 3 or 4. [00510] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. [00511] In certain embodiments, n is selected from those shown in the compounds of Table 2. [00512] As defined above and described herein, o is 0, 1, or 2. [00513] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, m is 2. [00514] In certain embodiments, o is selected from those shown in the compounds of Table 2. [00515] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is 1, X¹ is -CH₂-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-1:

I-cc-1 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00516] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is imidazolyl, o is 1, X¹ is -CH₂-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-2:

or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, and R² is as defined above and described in embodiments herein, both singly and in combination. [00517] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is imidazolyl, o is 1, X¹ is -CH₂-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-3:

I-cc-3 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, and R² is as defined above and described in embodiments herein, both singly and in combination. [00518] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is oxazolyl, o is 1, X¹ is -CH₂-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-4:

I-cc-4 or a pharmaceutically acceptable salt thereof, wherein each of PBM and L is as defined above and described in embodiments herein, both singly and in combination. [00519] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is 0, X¹ is a covalent bond, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-5:

or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00520] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is 1, X¹ is -O-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-6:

or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00521] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is 1, X¹ is -NR-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-7:

I-cc-7 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00522] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is 1, X¹ is -CF2-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-8:

or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00523] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is

X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-9:

or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00524] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is pyridyl, o is 1, X¹ is -CH₂-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-10:

I-cc-10 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00525] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is pyridyl, o is 1, X¹ is -CH₂-, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-11:

I-cc-11 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00526] In some embodiments, the present invention provides a compound of formula I-cc, wherein Ring A is benzo, o is 1, X¹, X² and X³ are -C(O)-, and Z¹ and Z² are carbon atoms as shown, to provide a compound of formula I-cc-12:

I-cc-12 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. _[00527] In some embodiments, the present invention provides a compound of formula I-cc, wherein Z¹ a

are -C(O)- as shown, to provide a compound of formula I-cc-13:

I-cc-13 or a pharmaceutically acceptable salt thereof, wherein each of PBM, L, R¹, and m is as defined above and described in embodiments herein, both singly and in combination. [00528] In some embodiments, the present invention provides a compound of formula I-dd, wherein X¹ and X⁴ are -CH₂-, and X² and X³ are -C(O)- as shown, to provide a compound of formula I-dd-1:

or a pharmaceutically acceptable salt thereof, wherein each of Ring C, L, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00529] In some embodiments, the present invention provides a compound of formula I-dd, wherein X¹ is -CH₂-, X⁴ is a covalent bond, and X² and X³ are -C(O)- as shown, to provide a compound of formula I-dd-2:

or a pharmaceutically acceptable salt thereof, wherein each of Ring C, L¹, R¹, R², and m is as defined above and described in embodiments herein, both singly and in combination. [00530] In some embodiments, LBM is selected from those in Table 2. [00531] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a RPN13 binding moiety thereby forming a compound of formula I-ee:

I-ee or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables A, Y, and Z is as described and defined in WO 2019/165229, the entirety of each of which is herein incorporated by reference. [00532] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a Ubr1 binding moiety as described in Shanmugasundaram, K. et al, J. Bio. Chem. 2019, doi: 10.1074/jbc.AC119.010790, the entirety of each of which is herein incorporated by reference, thereby forming a compound of formula I-ff-1 or I-ff-2:

I-ff-2 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein. [00533] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a CRBN binding moiety thereby forming a compound of formula I-gg:

I-gg or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R₁, R₂, R₃, R₄, R₅, Q, X, and n is as described and defined in US 2019/276474, the entirety of each of which is herein incorporated by reference. [00534] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-hh-1, I-hh- 2, I-hh-3 or I-hh-4:

I-hh-3 I-hh-4 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables Y, A¹,and A³ is as described and defined in WO 2019/236483, the entirety of each of which is herein incorporated by reference. [00535] In some embodiments, the present invention provides a compound of Formula I, wherein LBM is a cereblon E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-ii-1 to I-ii-10:

or a compound of formula I-iiʹ-1 to I-iiʹ-10:

I-iiʹ-5 I-iiʹ-6

or a compound of formula I-

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables

, X, X₁, X₂, Y, R₁, R₃, R₃’, R₄, R₅, t, m and n is as defined and described in WO 2017/007612 and US 2018/0134684, the entirety of each of which is herein incorporated by reference. [00536] In some embodiments, the present invention provides a compound of Formula I, wherein LBM is a cereblon E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-jj-1, I-jj-2, I- jj-3, I-jj-4, I-jj-5, or I-jj-6 respectively:

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables A, G, G’, Q₁, Q₂, Q₃, Q₄, R, R’, W, X, Y, Z, , and n is as defined and described in WO 2016/197114 and US 2018/0147202, the entirety of each of which is herein incorporated by reference. [00537] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-kk-1, I-kk-2, I-kk-3, I-kk-4, I-kk-5, I-kk-6, I-kk-7, or I-kk-8:

I-kk-7 I-kk-8 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables Ar, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, A, L, x, y, and is as described and defined in WO 2017/161119, the entirety of each of which is herein incorporated by reference. [00538] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-ll-1, I-ll-2, I-ll-3, I-ll-4, or I-ll-5, respectively:

I-ll-3

or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables A¹, A², A³, R⁵, G and Z is as defined and described in WO 2017/176958. [00539] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-mmʹ-1, I- mmʹʹ-1, I-mmʹ-2, I-mmʹ-2, I-mmʹ-3, I-mmʹʹ-3, I-mmʹ-4, I-mmʹʹ-4, I-mmʹ-5 or I-mmʹʹ-5 respectively:

I-mmʹ-5 I-mmʹʹ-5 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables A¹, A², A³, R⁵, G and Z is as defined and described in WO 2017/176958, the entirety of which is herein incorporated by reference. [00540] In certain embodiments, the present invention provides a compound of Formula I, wherein LBM is an cereblon E3 ubiquitin ligase binding moiety, thereby forming a compound of formula I-nn-1:

I-nn-1 or a pharmaceutically acceptable salt thereof, wherein L and PBM is as defined above and described in embodiments herein, and wherein: each of X¹, X², and X³ is independently a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–,

R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR₂, or an optionally substituted C_1-4 aliphatic; each of R² is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or –N(R)S(O)₂R; Ring A is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7-membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; m is 0, 1, 2, 3 or 4; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4- 7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00541] In certain embodiments, the present invention provides a compound of formula I-ccc-1, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-nnʹ-1 or I-nnʹʹ-1:

I-nnʹʹ-1 or a pharmaceutically acceptable salt thereof, wherein PBM, L, Ring A, X¹, X², X³, R¹, R² and m are as described above. [00542] As defined above and described herein, each of X¹, X², and X³ is independently a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

. [00543] In some embodiments, X¹ is a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

. _[00544] In some embodiments, X¹ is selected from those depicted in Table 2, below. [00545] In some embodiments, X² is a covalent bond, –CH₂–, –C(O)–, –C(S)–, or

. [00546] In some embodiments, X² is selected from those depicted in Table 2, below. [00547] In some embodiments, X³ is a covalent bond, –

. [00548] In some embodiments, X³ is selected from those depicted in Table 2, below. [00549] As defined above and described herein, R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR2, or an optionally substituted C1-4 aliphatic. [00550] In some embodiments, R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR₂, or an optionally substituted C_1-4 aliphatic. _[00551] In some embodiments, R¹ is selected from those depicted in Table 2, below. [00552] As defined above and described herein, each of R² is independently hydrogen, –R⁶, halogen, – CN, –NO₂, –OR, -SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or – N(R)S(O)₂R. [00553] In some embodiments, R² is hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or – N(R)S(O)₂R. [00554] In some embodiments, R² is selected from those depicted in Table 2, below. [00555] As defined above and described herein, each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [00556] In some embodiments, R⁶ is an optionally substituted C_1-6 aliphatic group. In some embodiments, R⁶ is an optionally substituted phenyl. In some embodiments, R⁶ is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R⁶ is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. [00557] In some embodiments, R⁶ is selected from those depicted in Table 2, below. [00558] As defined above and described herein, Ring A is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7-membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5- membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur. [00559] In some embodiments Ring A is a fused 6-membered aryl containing 0-2 nitrogen atoms. In some embodiments Ring A is a fused 5 to 7-membered partially saturated carbocyclyl. In some embodiments Ring A is a fused 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur. In some embodiments Ring A is a fused 5- membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur. [00560] In some embodiments, Ring A is a fused phenyl. [00561] In some embodiments, Ring A is selected from those depicted in Table 2, below. [00562] As defined above and described herein, m is 0, 1, 2, 3 or 4. [00563] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. [00564] In some embodiments, m is selected from those depicted in Table 2, below. [00565] As defined above and described herein, each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00566] In some embodiments, R is hydrogen. In some embodiments, R is phenyl. In some embodiments, R is a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. [00567] In some embodiments, R is selected from those depicted in Table 2, below. [00568] In some embodiments,

In some embodiments, LBM is

embodiments,

some embodiments, LBM is

. , . [00569] In some embodiments, LBM is selected from those in Table 2 below. [00570] In some embodiments, the present invention provides a compound of formula I-aaa-1, wherein

shown, thereby providing a compound of formula I-aaa-10:

I-aaa-10 or a pharmaceutically acceptable salt thereof, wherein each of variables L, X¹, X², X³, R¹, R², Ring A, m, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00571] In some embodiments, the present invention provides the compound of formula I-aaa-1, wherein

shown, thereby providing a compound of formula I-aaa-11:

I-aaa-11 or a pharmaceutically acceptable salt thereof, wherein each of L, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00572] In some embodiments, the present invention provides a compound of formula I-aaa-1, wherein

shown, thereby providing a compound of formula I-aaa-12:

I-aaa-12 or a pharmaceutically acceptable salt thereof, wherein each of variables L, X¹, R¹, R², Ring A, m, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00573] In some embodiments, the present invention provides a compound of formula I-aaa-1, wherein

I-aaa-13 or a pharmaceutically acceptable salt thereof, wherein each of variables L, X¹, R¹, R², m, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00574] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is an cereblon E3 ubiquitin ligase binding moiety, thereby forming a compound of formula I-oo:

I-oo or a pharmaceutically acceptable salt thereof, wherein L and PBM is as defined above and described in embodiments herein, and wherein:

X¹, X⁶, and X⁷ are independently a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF3–, –

X³ and X⁵ are independently a bivalent moiety selected from a covalent bond, –CR₂–, –NR–, –O–, –S–, or –SiR₂–; X⁴ is a trivalent moiety selected from

, , , , ,

each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur; each R^3a is independently hydrogen, deuterium, R^A, halogen, –CN, –NO₂, –OR, -SR, -NR₂, - SiR₃, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)NR₂, -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, –N(R)S(O)₂R, - NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)NR₂, -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R; each R^A is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each R^7a is independently hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR₂, –P(O)(OR)₂, –P(O)(NR₂)OR, –P(O)(NR₂)₂, –Si(OH)R₂, –Si(OH)₂R, – SiR₃, or an optionally substituted C_1-4 aliphatic; or R^7a and X¹ or X³ are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; two R^7a groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur; two R^7a groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; Ring N is selected from 6 to 10-membered aryl or heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; L is a covalent bond or a bivalent, saturated or partially unsaturated, straight or branched C1-20 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -O-, -NR-, -CRF-, - CF2-, -C(O)-, -S-, -S(O)-, -S(O)₂-, -SiR2-, -Si(OH)R-, -Si(OH)₂-, -P(O)OR-, -P(O)R-, or -P(O)NR2; each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-11 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; L³ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, - C(O)-, -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S-, -S(O)₂- or -(C)=CH-; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4. [00575] As defined above and described herein, X¹, X⁶, and X⁷ are independently a bivalent moiety selected from a covalent bond, –CH₂–, –C(R)₂–, –C(O)–, –C(S)–, –CH(R)–, –CH(CF3)–, –P(O)(OR)–, –

_[00576] In some embodiments, one or more of X¹, X⁶, and X⁷ is a covalent bond. In some embodiments, one or more of X¹, X⁶, and X⁷ is –CH₂–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –CR₂–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –C(O)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –C(S)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –CH(R)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –CH(CF₃)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –P(O)(OR)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –P(O)(R)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –P(O)NR₂–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –S(O)–. In some embodiments, one or more of X¹, X⁶, and X⁷ is –S(O)₂–. In some embodiments, one or more

[00577] In some embodiments, X¹, X⁶, and X⁷ are independently selected from those depicted in Table 1 below. [00578] As defined above and described herein, X² is a carbon atom, nitrogen atom, or silicon atom. [00579] In some embodiments, X² is a carbon atom. In some embodiments, X² is a nitrogen atom. In some embodiments, X² is a silicon atom. _[00580] In some embodiments, X² is selected from those depicted in Table 1 below. [00581] As defined above and described herein, X³ and X⁵ are independently a bivalent moiety selected from –CH₂–, –CR₂–, –NR–, –CF₂–, –CHF–, –S–, –CH(R)–, –SiR₂–, or –O–. [00582] In some embodiments, one or more of X³ and X⁵ is –CH₂–. In some embodiments, one or more of X³ and X⁵ is –CR₂–. In some embodiments, one or more of X³ and X⁵ is –NR–. In some embodiments, one or more of X³ and X⁵ is –CF₂–. In some embodiments, one or more of X³ and X⁵ is –CHF–. In some embodiments, one or more of X³ and X⁵ is –S–. In some embodiments, one or more of X³ and X⁵ is – CH(R)–. In some embodiments, one or more of X³ and X⁵ is –SiR₂–. In some embodiments, one or more of X³ and X⁵ is –O–. [00583] In some embodiments, X³ and X⁵ are independently selected from those depicted in Table 1 below. [00584] As defined above and described herein, X⁴ is a trivalent moiety selected from

,

[00585] In some embodiments, X⁴ is

. In some embodiments, X⁴ is

. In some embodiments, X⁴ is . In some embodiments, X⁴ is

. [00586] In some embodiments, X⁴ is selected from those depicted in Table 1 below. [00587] As defined above and described herein, each R^3a is independently hydrogen, deuterium, R^A, halogen, –CN, –NO₂, –OR, –Si(OH)₂R, –Si(OH)R2, -SR, -NR2, - SiR3, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR2, -C(O)N(R)OR, -C(R)₂N(R)C(O)R, - C(R)₂N(R)C(O)NR2, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)₂, -OP(O)(OR)NR2, -OP(O)(NR2)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, –N(R)S(O)₂R, -NP(O)R2, -N(R)P(O)(OR)₂, - N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)₂, or –N(R)S(O)₂R. [00588] In some embodiments, R^3a is hydrogen. In some embodiments, R^3a is deuterium. In some embodiments, R^3a is R^A. In some embodiments, R^3a is halogen. In some embodiments, R^3a is –CN. In some embodiments, R^3a is –NO₂. In some embodiments, R^3a is –OR. In some embodiments, R^3a is – Si(OH)₂R. In some embodiments, R^3a is –Si(OH)R2. In some embodiments, R^3a is –SR. In some embodiments, R^3a is -NR2. In some embodiments, R^3a is –SiR3. In some embodiments, R^3a is -S(O)₂R. In some embodiments, R^3a is -S(O)₂NR2. In some embodiments, R^3a is –S(O)R. In some embodiments, R^3a is –C(O)R. In some embodiments, R^3a is - C(O)OR. In some embodiments, R^3a is –C(O)NR₂. In some embodiments, R^3a is –C(O)N(R)OR. In some embodiments, R^3a is -C(R)₂N(R)C(O)R. In some embodiments, R^3a is -C(R)₂N(R)C(O)NR₂. In some embodiments, R^3a is –OC(O)R. In some embodiments, R^3a is –OC(O)NR₂. In some embodiments, R^3a is - OP(O)R₂. In some embodiments, R^3a is -OP(O)(OR)₂. In some embodiments, R^3a is -OP(O)(OR)NR₂. In some embodiments, R^3a is -OP(O)(NR₂)₂-. In some embodiments, R^3a is –N(R)C(O)OR. In some embodiments, R^3a is –N(R)C(O)R. In some embodiments, R^3a is –N(R)C(O)NR₂. In some embodiments, R^3a is -NP(O)R₂. In some embodiments, R^3a is -N(R)P(O)(OR)₂. In some embodiments, R^3a is - N(R)P(O)(OR)NR2. In some embodiments, R^3a is -N(R)P(O)(NR2)₂. In some embodiments, R^3a is – N(R)S(O)₂R. [00589] In some embodiments, R^3a is selected from those depicted in Table 1 below. [00590] As defined generally above, each R^7a is independently hydrogen, deuterium, halogen, –CN, – OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, –P(O)(R)₂, -P(O)(OR)₂, -P(O)(NR2)OR, -P(O)(NR2)₂, -Si(OH)R2, - Si(OH)₂R, -SiR3, or an optionally substituted C1-4 aliphatic, or R^7a and X¹ or X³ are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or two R^7a groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or two R^7a groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. [00591] In some embodiments, R^7a is hydrogen. In some embodiments, R^7a is deuterium. In some embodiments, R^7a is halogen. In some embodiments, R^7a is -CN. In some embodiments, R^7a is -OR. In some embodiments, R^7a is -SR. In some embodiments, R^7a is –S(O)R. In some embodiments, R^7a is – S(O)₂R. In some embodiments, R^7a is –NR₂. In some embodiments, R^7a is –Si(R)₃. In some embodiments, R^7a is –P(O)(R)₂. In some embodiments, R^7a is -P(O)(OR)₂. In some embodiments, R^7a is -P(O)(NR₂)OR. In some embodiments, R^7a is -P(O)(NR₂)₂. In some embodiments, R^7a is -Si(OH)R₂. In some embodiments, R^7a is -Si(OH)₂R. In some embodiments, R^7a is an optionally substituted C_1-4 aliphatic. In some embodiments, R^7a and X¹ or X³ are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R^7a groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R^7a groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R^7a groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. [00592] In some embodiments, R^7a is selected from hydrogen, halogen, -CN, -OR, -NR2, or C1-4 alkyl. In some embodiments, R^7a is selected from hydrogen, halogen, -CN, or C1-4 alkyl. In some embodiments, R⁷ is fluoro. In some embodiments, two R^7a groups on the same carbon are optionally taken together with their intervening atoms to form a 3- or 4-membered spiro fused ring. [00593] In some embodiments, R⁷ is selected from those depicted in Table 1 below. [00594] As defined above and described herein, Ring N is a ring selected from 6 to 10-membered aryl or heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7- membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; [00595] In some embodiments, Ring N is a 6 to 10-membered aryl. In some embodiments, Ring N is a 6 to 10-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Ring N is a 5 to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, Ring N is 5 to 7-membered saturated or partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring N is 5-membered heteroaryl with 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. [00596] In some embodiments, Ring N is isoquinoline. In some embodiments, Ring N is imidazo[1,2- a]pyridine. [00597] In some embodiments, Ring N is selected from those depicted in Table 1 below. [00598] As defined above and described herein, Ring M is selected from

, , a

[00599] In some embodiments, Ring

In some embodiments, Ring M is

In some embodiments, Ring M is

O . In some embodiments, Ring M is O . In some embodiments, Ring M is

. In some embodiments, Ring M is . In some embodiments, Ring M is . In some embodiments, Ring M is . [00600] In some embodiments, Ring M is selected from those depicted in Table 1 below. [00601] As defined above and described here, L³ is a covalent bond or a C_1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, -C(O)-, -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S-, - S(O)₂- or -(C)=CH-; [00602] In some embodiments, L³ is a covalent bond. In some embodiments, L³ is a C_1-3 aliphatic. In some embodiments, L³ is –CH₂–. In some embodiments, L³ is –C(D)(H)-. In some embodiments, L³ is - C(D)₂–. In some embodiments, L³ is –CH₂CH₂–. In some embodiments, L¹ is –NR–. In some embodiments, L³ is –CH₂NR–. In some embodiments, L³ is or –O–. In some embodiments, L³ is –CH₂O– . In some embodiments, L³ is –S–. In some embodiments, L³ is -OC(O)-. In some embodiments, L³ is - C(O)O-. In some embodiments, L³ is -C(O)-. In some embodiments, L³ is -S(O)-. In some embodiments, L³ is -S(O)₂-,. In some embodiments, L³ is -NRS(O)₂-. In some embodiments, L³ is -S(O)₂NR-. In some embodiments, L³ is -NRC(O)-. In some embodiments, L³ is -C(O)NR-. [00603] In some embodiments, L³ is selected from those depicted in Table 1 below. [00604] As defined above and described herein, p is 0, 1, 2, 3 or 4. [00605] In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. [00606] In some embodiments, p is selected from those depicted in Table 1 below. [00607] As defined above and described herein, q is 0, 1, 2, 3 or 4. [00608] In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, q is 2. In some embodiments, q is 3. In some embodiments, q is 4. [00609] In some embodiments, q is selected from those depicted in Table 1 below. [ e

[00611] In some embodiments, the present invention provides a compound of formula I-aaa-1, wherein

shown, thereby providing a compound of formula I-aaa-14:

I-aaa-14 or a pharmaceutically acceptable salt thereof, wherein each of variables Ring M, Ring N, L, L³, R^3a, R^7a, p, q, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00612] In some embodiments, the present invention provides the compound of formula I-aaa-1, wherein

shown, thereby providing a compound of formula I-aaa-15:

I-aaa-15 or a pharmaceutically acceptable salt thereof, wherein each of L, R^3a, p, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00613] In some embodiments, the present invention provides a compound of formula I-aaa-1, wherein

I-aaa-16 or a pharmaceutically acceptable salt thereof, wherein each of variables L, R^3a, p, R^w, R^x, and R^y is as defined above and described in embodiments herein, both singly and in combination. [00614] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is human kelch-like ECH-associated protein 1 (KEAP1) thereby forming a compound of formula I-pp-1:

I-pp-1 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, both singly and in combination. [00615] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is KEAP1 binding moiety as recited in Lu et al., Euro. J. Med. Chem., 2018, 146:251-9, thereby forming a compound of formula I-pp-2:

I-pp-2 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, both singly and in combination. [00616] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is KEAP1-NRF2 binding moiety thereby forming a compound of formula I-pp-3 or I-pp-4:

I-pp-4 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R, R1, R5, and R8 is as described and defined in WO 2020/018788, the entirety of each of which is herein incorporated by reference. [00617] In certain embodiments, the present invention provides a compound of formula I, wherein LBM is KEAP1-NRF2 binding moiety as recited in Tong et al., "Targeted Protein Degradation via a Covalent Reversible Degrader Based on Bardoxolone", ChemRxiv 2020, thereby forming a compound of formula I-pp-5 or I-pp-6:

I-pp-5

I-pp-6 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, both singly and in combination. Degradation Inducing Moiety (DIM) [00618] In certain embodiments, the present invention provides a compound of formula I:

I or a pharmaceutically acceptable salt thereof, wherein L and PBM are as described above and herein, and DIM is a degradation inducing moiety selected from LBM, a lysine mimetic, or a hydrogen atom. [00619] In some embodiments, DIM is LBM as described above and herein. In some embodiments, DIM is a lysine mimetic. In some embodiments, the covalent attachment of ubiquitin to coronavirus protease protein is achieved through the action of a lysine mimetic. In some embodiments, upon the binding of a compound of formula I to coronavirus protease protein, the moiety that mimics a lysine undergoes ubiquitination thereby marking coronavirus protease protein for degradation via the Ubiquitin-Proteasome Pathway (UPP). [00620] In some embodiments, DIM is

. In some embodiments, DIM is

. In some embodiments,

[00621] In some embodiments, DIM is selected from those depicted in Table 2, below. [00622] In some embodiments, the present invention provides the compound of formula I as a compound of formula I-aaaa:

I-aaaa or a pharmaceutically acceptable salt thereof, wherein each of PBM and L is as defined above and described in embodiments herein, both singly and in combination. [00623] In some embodiments, the present invention provides the compound of formula I as a compound of formula I-aaaa-1:

I-aaaa-1 or a pharmaceutically acceptable salt thereof, wherein each of PBM and L is as defined above and described in embodiments herein, both singly and in combination. [00624] In some embodiments, the present invention provides the compound of formula I as a compound of formula I-aaaa-2:

I-aaaa-2 or a pharmaceutically acceptable salt thereof, wherein each of PBM and L is as defined above and described in embodiments herein, both singly and in combination. [00625] In certain embodiments, the present invention provides a compound of Formula I, wherein DIM is a lysine mimetic

, , or

thereby forming a compound of Formulae I-bbbb-1, I-bbbb-2, or I- bbbb-3, respectively:

I-bbbb-3 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R¹, R⁴, R⁵, A, B, E, Y, Yʹ, Z, Zʹ, and k are as defined and described in U.S. Pat. No.7,622,496, the entirety of each of which is herein incorporated by reference. Hydrogen Atom [00626] In some embodiments, DIM is a hydrogen atom. In some embodiments, the covalent attachment of ubiquitin to coronavirus protease protein is achieved through a provided compound wherein DIM is a hydrogen atom. In some embodiments, upon the binding of a compound of formula I to coronavirus protease protein, the moiety being hydrogen effectuates ubiquitination thereby marking coronavirus protease protein for degradation via the Ubiquitin-Proteasome Pathway (UPP). [00627] In some embodiments, DIM is selected from those depicted in Table 2, below. [00628] In some embodiments, the present invention provides the compound of formula I wherein DIM is a hydrogen atom, thereby forming a compound of formula I-cccc:

I-cccc or a pharmaceutically acceptable salt thereof, wherein each of PBM and L is as defined above and described in embodiments herein, both singly and in combination. Linker (L) [00629] As defined above and described herein, L is a bivalent moiety that connects PBM to LBM or PBM to DIM. [00630] In some embodiments, L is a bivalent moiety that connects PBM to LBM. In some embodiments, L is a bivalent moiety that connects PBM to DIM. In some embodiments, L is a bivalent moiety that connects PBM to a lysine mimetic. [00631] In some embodiments, L is a covalent bond or a bivalent, saturated or partially unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -O-, -N(R)-, –Si(R)₂–, –Si(OH)(R)–, –Si(OH)₂–, –P(O)(OR)–, –P(O)(R)–, –P(O)(NR₂)–, -S-, - OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)₂-, -N(R)S(O)₂-, -S(O)₂N(R)-, -N(R)C(O)-, -C(O)N(R)-, -

each –Cy– is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-11 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same atom are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur, and; r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. [00632] In some embodiments, L is selected from those depicted in Table 2, below. [00633] In some embodiments, each –Cy– is independently an optionally substituted bivalent phenylenyl. In some embodiments, each –Cy– is independently an optionally substituted 8-10 membered bicyclic arylenyl. In some embodiments, each –Cy– is independently an optionally substituted 4-7 membered saturated or partially unsaturated carbocyclylenyl. In some embodiments, each –Cy– is independently an optionally substituted 4-11 membered saturated or partially unsaturated spiro carbocyclylenyl. In some embodiments, each –Cy– is independently an optionally substituted 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl. In some embodiments, each –Cy– is independently an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each –Cy– is independently an optionally substituted 4-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each –Cy– is independently an optionally substituted 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each –Cy– is independently an optionally substituted 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each –Cy– is independently an optionally substituted 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [00634] In some embodiments, -Cy- is selected from those depicted in Table 2, below. [00635] In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, r is 2. In some embodiments, r is 3. In some embodiments, r is 4. In some embodiments, r is 5. In some embodiments, r is 6. In some embodiments, r is 7. In some embodiments, r is 8. In some embodiments, r is 9. In some embodiments, r is 10. [00636] In some embodiments, r is selected from those depicted in Table 2, below. [00637] In some embodiments, L is

. In some embodiments, L is

embodiments, L is . In some embodiments, L is

s

. [00638] In some embodiments, L is selected from those depicted in Table 2, below. [00639] Without limitation, the point of attachment of L to PBM and DIM can be, for example when L i

[00640] In some embodiments, a provided compound or pharmaceutically acceptable salt thereof, is selected from those wherein

selected from any of those in Table A below, and L is selected from any of those in Table B below. [00641] In some embodiments, a provided compound or pharmaceutically acceptable salt thereof, is s

of those in Table A below, and L is selected from any of those in Table B below. [00642] In some embodiments, a provided compound or pharmaceutically acceptable salt thereof, is selected from those wherein

selected from any of those in Table A below, and L is selected from any of those in Table B below. Table A. Exemplified E3 Ligase Binding Moiety (LBM)

[00643] In some embodiments, the present invention provides a compound having PBM described and disclosed herein, LBM set forth in Table A above, and a linker set forth in Table B above, or a pharmaceutically acceptable salt thereof. [00644] Exemplary compounds of the invention are set forth in Table 2, below. Table 2. Exemplary Compounds

[00645] In some embodiments, the present invention provides a compound set forth in Table 2, above, or a pharmaceutically acceptable salt thereof. 4. General Methods of Providing the Present Compounds [00646] The compounds of this invention may be prepared or isolated in general by synthetic and/or semi-synthetic methods known to those skilled in the art for analogous compounds and by methods described in detail in the Examples, herein. [00647] In the Schemes below, where a particular protecting group, leaving group, or transformation condition is depicted, one of ordinary skill in the art will appreciate that other protecting groups, leaving groups, and transformation conditions are also suitable and are contemplated. Such groups and transformations are described in detail in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, M. B. Smith and J. March, 5^th Edition, John Wiley & Sons, 2001, Comprehensive Organic Transformations, R. C. Larock, 2^nd Edition, John Wiley & Sons, 1999, and Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, the entirety of each of which is hereby incorporated herein by reference. [00648] As used herein, the phrase “oxygen protecting group” includes, for example, carbonyl protecting groups, hydroxyl protecting groups, etc. Hydroxyl protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, the entirety of each of which is herein incorporated by reference. Examples of suitable hydroxyl protecting groups include, but are not limited to, esters, allyl ethers, ethers, silyl ethers, alkyl ethers, arylalkyl ethers, and alkoxyalkyl ethers. Examples of such esters include formates, acetates, carbonates, and sulfonates. Specific examples include formate, benzoyl formate, chloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, p-chlorophenoxyacetate, 3- phenylpropionate, 4-oxopentanoate, 4,4-(ethylenedithio)pentanoate, pivaloate (trimethylacetyl), crotonate, 4-methoxy-crotonate, benzoate, p-benylbenzoate, 2,4,6-trimethylbenzoate, carbonates such as methyl, 9- fluorenylmethyl, ethyl, 2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, 2-(phenylsulfonyl)ethyl, vinyl, allyl, and p-nitrobenzyl. Examples of such silyl ethers include trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triisopropylsilyl, and other trialkylsilyl ethers. Alkyl ethers include methyl, benzyl, p- methoxybenzyl, 3,4-dimethoxybenzyl, trityl, t-butyl, allyl, and allyloxycarbonyl ethers or derivatives. Alkoxyalkyl ethers include acetals such as methoxymethyl, methylthiomethyl, (2-methoxyethoxy)methyl, benzyloxymethyl, beta-(trimethylsilyl)ethoxymethyl, and tetrahydropyranyl ethers. Examples of arylalkyl ethers include benzyl, p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl, O-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, and 2- and 4-picolyl. [00649] Amino protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, the entirety of each of which is herein incorporated by reference. Suitable amino protecting groups include, but are not limited to, aralkylamines, carbamates, cyclic imides, allyl amines, amides, and the like. Examples of such groups include t-butyloxycarbonyl (BOC), ethyloxycarbonyl, methyloxycarbonyl, trichloroethyloxycarbonyl, allyloxycarbonyl (Alloc), benzyloxocarbonyl (CBZ), allyl, phthalimide, benzyl (Bn), fluorenylmethylcarbonyl (Fmoc), formyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, phenylacetyl, trifluoroacetyl, benzoyl, and the like. [00650] In the schemes below, where a provided compound is formed having a reactive moiety (e.g., amine, alcohol, etc.), it is not shown but it is generally appreciated and well known by those having ordinary skill in the art that the reactivity of said reactive moiety may be masked by employing a suitable protecting group that can thereafter be removed in situ or during a separate synthetic step. [00651] In certain embodiments, compounds of the present invention are generally prepared according to Scheme 1 set forth below: Scheme 1: Synthesis of Compounds of Formula I

[00652] As depicted in Scheme 1, above, amine A-1 is coupled to acid A-2 using the coupling agent HATU in the presence of the base DIPEA in DMF to form a compound of formula I with a linker comprising an amide bond. The squiggly bond, , represents the portion of the linker between PBM and the terminal amino group of A-1 or the portion of the linker between DIM and the terminal carboxyl group of A-2, respectively. Additionally, an amide bond can be formed using coupling reagents known in the art such as, but not limited to DCC, DIC, EDC, HBTU, HCTU, PyAOP, PyBrOP, BOP, BOP-Cl, DEPBT, T3P, TATU, TBTU, TNTU, TOTU, TPTU, TSTU, or TDBTU. [00653] In certain embodiments, compounds of the present invention are generally prepared according to Scheme 2 set forth below: Scheme 2: Synthesis of Compounds of Formula I

[00654] As depicted in Scheme 2, above, amine A-1 is coupled to acid A-2 using the coupling agent PyBOP in the presence of the base DIPEA in DMF to form a compound of formula I with a linker comprising an amide bond. The squiggly bond, , represents the portion of the linker between PBM and the terminal amino group of A-1 or the portion of the linker between DIM and the terminal carboxyl group of A-2, respectively. Additionally, an amide bond can be formed using coupling reagents known in the art such as, but not limited to DCC, DIC, EDC, HBTU, HCTU, PyAOP, PyBrOP, BOP, BOP-Cl, DEPBT, T3P, TATU, TBTU, TNTU, TOTU, TPTU, TSTU, or TDBTU. [00655] In certain embodiments, compounds of the present invention are generally prepared according to Scheme 3 set forth below: Scheme 3: Synthesis of Compounds of Formula I

[00656] As depicted in Scheme 3, above, acid A-3 is coupled to amine A-4 using the coupling agent HATU in the presence of the base DIPEA in DMF to form a compound of formula I with a linker comprising an amide bond. The squiggly bond, , represents the portion of the linker between PBM and the terminal carboxyl group of A-3 or the portion of the linker between DIM and the terminal amino group of A-4, respectively. Additionally, an amide bond can be formed using coupling reagents known in the art such as, but not limited to DCC, DIC, EDC, HBTU, HCTU, PyAOP, PyBrOP, BOP, BOP-Cl, DEPBT, T3P, TATU, TBTU, TNTU, TOTU, TPTU, TSTU, or TDBTU. [00657] In certain embodiments, compounds of the present invention are generally prepared according to Scheme 4 set forth below: Scheme 4: Synthesis of Compounds of Formula I

[00658] As depicted in Scheme 4, above, acid A-3 is coupled to amine A-4 using the coupling agent PyBOP in the presence of the base DIPEA in DMF to form a compound of formula I with a linker comprising an amide bond. The squiggly bond, , represents the portion of the linker between PBM and the terminal carboxyl group of A-3 or the portion of the linker between DIM and the terminal amino group of A-4, respectively. Additionally, an amide bond can be formed using coupling reagents known in the art such as, but not limited to DCC, DIC, EDC, HBTU, HCTU, PyAOP, PyBrOP, BOP, BOP-Cl, DEPBT, T3P, TATU, TBTU, TNTU, TOTU, TPTU, TSTU, or TDBTU. [00659] In certain embodiments, compounds of the present invention are generally prepared according to Scheme 5 set forth below: Scheme 5: Synthesis of Compounds of Formula I

[00660] As depicted in Scheme 5, above, an S_NAr displacement of fluoride A-6 by amine A-5 is effected in the presence of the base DIPEA in DMF to form a compound of formula I with a linker comprising a secondary amine. The squiggly bond, , represents the portion of the linker between PBM and the terminal amino group of A-5. [00661] In certain embodiments, compounds of the present invention are generally prepared according to Scheme 6 set forth below: Scheme 6: Synthesis of Compounds of Formula I

[00662] As depicted in Scheme 6, above, an S_NAr displacement of fluoride A-7 by amine A-8 is effected in the presence of the base DIPEA in DMF to form a compound of formula I with a linker comprising a secondary amine. The squiggly bond, , represents the portion of the linker between DIM and the terminal amino group of A-8. Scheme 7: Synthesis of Compounds of Formula I

[00663] As depicted in Scheme 7, above, reductive amination of the mixture of aldehyde A-9 and amine A-10 is effected in the presence of NaHB(OAc)₃ and KOAc in DMF/THF to form a compound of formula I with a linker comprising a secondary amine. The squiggly bond, , represents the portion of the linker between DIM and the terminal amino group of A-8. [00664] One of skill in the art will appreciate that various functional groups present in compounds of the invention such as aliphatic groups, alcohols, carboxylic acids, esters, amides, aldehydes, halogens and nitriles can be interconverted by techniques well known in the art including, but not limited to reduction, oxidation, esterification, hydrolysis, partial oxidation, partial reduction, halogenation, dehydration, partial hydration, and hydration. “March’s Advanced Organic Chemistry”, 5^th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entirety of which is incorporated herein by reference. Such interconversions may require one or more of the aforementioned techniques, and certain methods for synthesizing compounds of the invention are described below in the Exemplification. 5. Uses, Formulation and Administration Pharmaceutically acceptable compositions [00665] According to another embodiment, the invention provides a composition comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of compound in compositions of this invention is such that is effective to measurably degrade and/or inhibit a coronavirus protease protein, or a mutant thereof, in a biological sample or in a patient. In certain embodiments, the amount of compound in compositions of this invention is such that is effective to measurably degrade and/or inhibit a coronavirus protease protein, or a mutant thereof, in a biological sample or in a patient. In certain embodiments, a composition of this invention is formulated for administration to a patient in need of such composition. In some embodiments, a composition of this invention is formulated for oral administration to a patient. [00666] The compounds and compositions, according to the method of the present invention, may be administered using any amount and any route of administration effective for treating or lessening the severity of a viral disease. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the infection, the particular agent, its mode of administration, and the like. Compounds of the invention are preferably formulated in dosage unit form for ease of administration and uniformity of dosage. The expression "dosage unit form" as used herein refers to a physically discrete unit of agent appropriate for the patient to be treated. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific effective dose level for any particular patient or organism will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed, and like factors well known in the medical arts. [00667] The term “patient”, as used herein, means an animal, preferably a mammal, and most preferably a human. [00668] The term “pharmaceutically acceptable carrier, adjuvant, or vehicle” refers to a non-toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that may be used in the compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene- polyoxypropylene-block polymers, polyethylene glycol and wool fat. [00669] A “pharmaceutically acceptable derivative” means any non-toxic salt, ester, salt of an ester or other derivative of a compound of this invention that, upon administration to a recipient, is capable of providing, either directly or indirectly, a compound of this invention or an inhibitorily or degratorily active metabolite or residue thereof. [00670] As used herein, the term “inhibitorily active metabolite or residue thereof” means that a metabolite or residue thereof is also an inhibitor of a coronavirus protease protein, or a mutant thereof. [00671] As used herein, the term “degratorily active metabolite or residue thereof” means that a metabolite or residue thereof is also a degrader of a coronavirus protease protein, or a mutant thereof. [00672] Compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. [00673] For this purpose, any bland fixed oil may be employed including synthetic mono- or di- glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation. [00674] Pharmaceutically acceptable compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added. [00675] Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. [00676] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. [00677] Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. [00678] In order to prolong the effect of a compound of the present invention, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compound then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compound form is accomplished by dissolving or suspending the compound in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compound in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of compound to polymer and the nature of the particular polymer employed, the rate of compound release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the compound in liposomes or microemulsions that are compatible with body tissues. [00679] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar--, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. [00680] Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like. [00681] The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. [00682] Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, and eye drops are also contemplated as being within the scope of this invention. Additionally, the present invention contemplates the use of transdermal patches, which have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. [00683] Alternatively, pharmaceutically acceptable compositions of this invention may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax and polyethylene glycols. [00684] Pharmaceutically acceptable compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. [00685] Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. [00686] For topical applications, provided pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of compounds of this invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, provided pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. [00687] Most preferably, pharmaceutically acceptable compositions of this invention are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, pharmaceutically acceptable compositions of this invention are administered without food. In other embodiments, pharmaceutically acceptable compositions of this invention are administered with food. [00688] The amount of compounds of the present invention that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the host treated, the particular mode of administration. Preferably, provided compositions should be formulated so that a dosage of between 0.01 - 100 mg/kg body weight/day of the compound can be administered to a patient receiving these compositions. In certain embodiments, the compounds of the invention may be administered orally or parenterally at dosage levels of about 0.01 mg/kg to about 50 mg/kg and preferably from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect. Uses of Compounds and Pharmaceutically Acceptable Compositions [00689] Compounds and compositions described herein are generally useful for the degradation and/or inhibition of coronavirus protease activity. [00690] The activity of a compound utilized in this invention as a degrader and/or inhibitor of coronavirus 3CL protease or a mutant thereof, may be assayed in vitro, in vivo or in a cell line. In vitro assays include assays that determine inhibition of either the activity and/or the subsequent functional consequences of activated coronavirus 3CL protease or a mutant thereof. Alternate in vitro assays quantitate the ability of the inhibitor to bind to coronavirus 3CL protease. Inhibitor binding may be measured by radiolabeling the inhibitor prior to binding, isolating the inhibitor/ coronavirus 3CL protease complex and determining the amount of radiolabel bound. Alternatively, inhibitor binding may be determined by running a competition experiment where new inhibitors are incubated with coronavirus 3CL protease bound to known radioligands. Representative in vitro and in vivo assays useful in assaying coronavirus 3CL protease inhibitors include those described and disclosed in, e.g., Pullaiya et al., J. Med. Chem.2016, 59(14):6595-9929; Grum-Tokars et al., Virus Res.2008, 133(1):63-73; and Hamill et al., Biol. Chem.2006, 387(8):1063-1074. Detailed conditions for assaying a compound utilized in this invention as a degrader and/or inhibitor of coronavirus 3CL protease or a mutant thereof, are set forth in the Examples below. [00691] As used herein, the terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment may be administered after one or more symptoms have developed. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of possible viral transmission and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence. [00692] Provided compounds are degraders and/or inhibitors of coronavirus 3CL protease and are therefore useful for treating one or more disorders associated with activity of coronavirus infection. Thus, in certain embodiments, the present invention provides a method for treating a coronavirus-mediated disorder comprising the step of administering to a patient in need thereof a compound of the present invention, or pharmaceutically acceptable composition. [00693] As used herein, the terms “coronavirus-mediated” disorders, diseases, and/or conditions as used herein means any disease or other deleterious condition in which coronavirus infection is known to play a role. Accordingly, another embodiment of the present invention relates to treating or lessening the severity of one or more diseases in which coronavirus are known to play a role. [00694] According to another embodiment, the invention relates to a method of inhibiting or degrading coronavirus 3CL protease, or a mutant thereof, activity in a biological sample comprising the step of contacting said biological sample with a compound of this invention, or a composition comprising said compound. [00695] The term “biological sample”, as used herein, includes, without limitation, cell cultures or extracts thereof; biopsied material obtained from a mammal or extracts thereof; and blood, saliva, urine, feces, semen, tears, or other body fluids or extracts thereof. [00696] According to another embodiment, the invention relates to a method of degrading and/or inhibiting coronavirus protease activity, or a mutant thereof, in a patient comprising the step of administering to said patient a compound of the present invention, or a composition comprising said compound. In other embodiments, the present invention provides a method for treating a disorder mediated by coronavirus infection, in a patient in need thereof, comprising the step of administering to said patient a compound according to the present invention or pharmaceutically acceptable composition thereof. Such disorders are described in detail herein. [00697] Provided compounds are degraders and/or inhibitors of coronavirus 3CL protease or a mutant thereof and are therefore useful for treating one or more disorders associated with coronavirus infection. Thus, in certain embodiments, the present invention provides a method for treating coronavirus disease 2019 (COVID-19) comprising the step of administering to a patient in need thereof a compound of the present invention, or pharmaceutically acceptable composition thereof. [00698] In another aspect, the present disclosure provides methods of treating a condition or disease by administering a therapeutically effective amount of a provided compound to an individual, e.g., a human, in need thereof. The disease or condition of interest is treatable by degradation of coronavirus 3CL protease, for example, in a subject infected with a coronavirus. [00699] In another embodiment, the present invention provides a compound for use in therapy. [00700] In another embodiment, the present invention provides a compound for use in the treatment of a coronavirus infection (e.g., SARS-CoV-2 infection). [00701] In another embodiment, the present invention provides a compound for use in the manufacture of a medicament for use in the treatment of a coronavirus infection in a human. [00702] The provided compounds or pharmaceutically acceptable salts thereof, are believed to have activity in preventing, halting or reducing the effects of a coronavirus by inhibiting the viral 3CL protease or mutant thereof, thereby interfering with or preventing the polyprotein processing of the translated viral genome, in the host cell, rendering the virus unable to replicate. [00703] Accordingly, herein is provided a method of treating a disease or condition susceptible to coronavirus protease inhibition or degradation in a mammal, including administering to said mammal a therapeutically effective amount of a provided compound or a pharmaceutically acceptable salt thereof. In one embodiment, the coronavirus protease is coronavirus 3CL protease or mutant thereof. In one embodiment the disease or condition is COVID-19. [00704] In another aspect of the present invention, there is provided a method of inhibiting coronavirus 3CL protease or mutant thereof in a mammal, including administering to said mammal a therapeutically effective amount of a provided compound or a pharmaceutically acceptable salt thereof. In one embodiment, the mammal is a human. [00705] In a further aspects, the present invention provides for a method of treating coronavirus infection or an associated pathophysiology. In some embodiments, the present invention provides a method for treating one or more coronavirus-mediated disorders, diseases, and/or conditions wherein the disorder, disease, or conditions is a respiratory disorder, including COPD, asthma, fibrosis, chronic asthma and acute asthma, lung disease secondary to environmental exposures, acute lung infection, chronic lung infection, a1 antitrypsin disease, cystic fibrosis, or an autoimmune disease. [00706] In some embodiments, the present invention provides a method of treating a respiratory disorder, including COPD, asthma, fibrosis, chronic asthma and acute asthma, lung disease secondary to environmental exposures, acute lung infection, chronic lung infection, a1 antitrypsin disease, cystic fibrosis and an autoimmune disease, which comprises administering to a human in need thereof, a provided compound or a pharmaceutically acceptable salt thereof. [00707] In one aspect, this invention relates to a method of treating COPD, which comprises administering to a human in need thereof, a provided compound or a pharmaceutically acceptable salt thereof. [00708] In yet another aspect, this invention provides for the use of a provided compound or a pharmaceutically acceptable salt thereof, for the treatment of a respiratory disorder, including COPD, asthma, fibrosis, chronic asthma and acute asthma, lung disease secondary to environmental exposures, acute lung infection, chronic lung infection, a1 antitrypsin disease, cystic fibrosis and an autoimmune disease. [00709] In one aspect, the present invention relates to the use of a provided or a pharmaceutically acceptable salt thereof, for the treatment of COPD. [00710] In a further aspect, this invention relates to the use of a provided compound or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of a respiratory disorder, including COPD, asthma, fibrosis, chronic asthma and acute asthma, lung disease secondary to environmental exposures, acute lung infection, chronic lung infection, alpha-1 antitrypsin disease, cystic fibrosis and an autoimmune disease. [00711] In one aspect, the present invention relates to use of a provided compound or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of COPD. [00712] In a further aspect, the present invention relates to a provided compound or a pharmaceutically acceptable salt thereof, for use in medical therapy. In some embodiments, the present invention relates to a provided compound or a pharmaceutically acceptable salt thereof, for use in therapy, specifically for use in the treatment of a respiratory disorder, including COPD, asthma, fibrosis, chronic asthma and acute asthma, lung disease secondary to environmental exposures, acute lung infection, chronic lung infection, a1 antitrypsin disease, cystic fibrosis and an autoimmune disease. [00713] In one aspect, the present invention relates to a provided compound or a pharmaceutically acceptable salt thereof, for use in the treatment of COPD. [00714] In another embodiment of the present invention, there is provided a method of treating a virus infection in a subject suffering from the virus infection comprising administering to the subject a selective chemical inhibitor or degrader of a 3CL protease enzyme, wherein the inhibitor or degrader comprises a provided compound. [00715] The present invention is directed to compounds, compositions and pharmaceutical compositions that have utility as novel treatments and/or preventative therapies for coronavirus infections. While not wanting to be bound by any particular theory, it is thought that the present compounds are able to inhibit the activity of coronavirus self-cleaving enzymes - 3CL (3C-like) proteases in coronavirus - which play an important role in processing polyprotein precursor proteins into functional viral proteins and enzymes. Inhibition or degradation of 3CL proteases are therefore expected to reduce the ability of the coronavirus to replicate inside a host cell. By disrupting the ability of the coronavirus to process its polyprotein precursors after the viral genome has been translated in a host cell, disease and symptoms resulting from coronavirus infections can be treated and/or prevented. [00716] Therefore, in another embodiment of the present invention, there is provided a method of treating or preventing a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject an inhibitor or degrader of a 3CL protease enzyme or mutant thereof, wherein the inhibitor or degrader is a provided compound. [00717] In another embodiment of the present invention, there is provided a method of treating a coronavirus infection in a subject suffering from the another virus infection (e.g., rhinovirus infection) comprising administering to the subject an inhibitor or degrader of 3CL protease wherein the inhibitor or degrader is a provided compound. [00718] In one embodiment of the present invention, the compounds described herein are useful for preventing or treating viral infections in a subject caused by a single-stranded RNA virus. [00719] An RNA virus is a virus that has RNA (ribonucleic acid) as its genetic material. This nucleic acid is usually single-stranded RNA (ssRNA). RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. As such, purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. Purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs. [00720] In another embodiment of the present invention, there is provided a method of treating or preventing infection from an RNA-based virus in a subject suffering from the virus infection comprising administering to the subject an inhibitor or degrader of a 3CL protease enzyme wherein the inhibitor or degrader is a provided compound. [00721] In one embodiment of the present invention, the provided compounds described herein are useful for preventing or treating viral infections in a subject caused by a positive-sense, single-stranded RNA virus. [00722] In one embodiment of the present invention, the provided compounds described herein are useful for preventing or treating viral infections in a subject caused by a negative-sense, single-stranded RNA virus. [00723] In some embodiments, provided is a method for treating a viral infection in a subject mediated at least in part by a virus in the coronaviridae family of viruses, comprising administering to the subject a composition comprising a provided compound or a pharmaceutically acceptable salt thereof. In certain embodiments, the coronaviridae virus is SARS-CoV-2. [00724] In yet another aspect, another embodiment of the present invention provides a method of inhibiting progression of a viral infection in a subject at risk for infection with a virus in the coronaviridae family of viruses, comprising administering to the subject a therapeutically effective amount of a provided compound or a pharmaceutically acceptable salt thereof. In certain embodiments, the coronaviridae virus is SARS-CoV-2. [00725] In yet another aspect, another embodiment of the present invention provides a method of preventing a viral infection in a subject at risk for infection from a virus in the coronaviridae family of viruses, comprising administering to the subject a therapeutically effective amount of a provided compound or a pharmaceutically acceptable salt thereof. In certain embodiments, the coronaviridae virus is SARS- CoV-2. [00726] In yet another aspect, another embodiment of the present invention provides a method of treating a virus infection in a subject suffering from said virus infection, wherein the virus is in the coronaviridae family of viruses, comprising administering to the subject a therapeutically effective amount of a provided compound or a pharmaceutically acceptable salt thereof. In certain embodiments, the coronaviridae virus is SARS-CoV-2. [00727] In some embodiments, the present invention provides a method of treating a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject a provided compound or a pharmaceutically acceptable salt thereof. [00728] In some embodiments, the present invention provides a method of preventing a virus infection in a subject comprising administering to the subject a provided compound or a pharmaceutically acceptable salt thereof. [00729] In some embodiments, the present invention provides a method of treating a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject a chemical inhibitor or degrader of coronavirus 3CL protease selected from the group consisting of a 229E 3CL protease, a NL63 3CL protease, a OC43 3CL protease, a HKU1 3CL protease, a SARS-CoV 3CL protease, a SARS-CoV-23CL protease, and a MERS-CoV 3CL protease. [00730] In some embodiments, the present invention provides a method of treating a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject a chemical inhibitor or degrader of a coronavirus 229E 3CL protease. [00731] In some embodiments, the present invention provides a method of treating a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject a chemical inhibitor or degrader of a coronavirus OC433CL protease. [00732] In some embodiments, the present invention provides a method of treating a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject a chemical inhibitor or degrader of a coronavirus HKU13CL protease. [00733] In some embodiments, the present invention provides a method of treating a coronavirus infection in a subject suffering from the coronavirus infection comprising administering to the subject a chemical inhibitor or degrader of a coronavirus SARS-CoV-23CL protease. [00734] Compounds, methods and pharmaceutical compositions for treating coronavirus infections, by administering a provided compound in therapeutically effective amounts are disclosed. Methods for preparing the provides compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of coronavirus infections such as those caused by SARS-CoV-2 are disclosed. [00735] In other embodiments, the compounds described herein are useful for treating viral infections in a subject where the infection is caused by a virus belonging to the coronaviridae family (e.g., SARS- CoV-2). [00736] In other embodiments, the compounds described herein are useful for treating viral infections in a subject where the infection is caused by any one or more viruses selected from the group consisting of rhinovirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2), common coronaviridae (including but not limited to OC43, HKU1, 229e and NL63), enterovirus, poliovirus, coxsackievirus, hepatitis A virus, foot-and-mouth disease virus (FMDV), and calicivirus. [00737] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by any of the human coronaviruses. [00738] In other embodiments, the compound described herein are useful for treating infections in a subject wherein the infection is caused by any of the human coronaviruses 229E, NL63, OC43, HKU1, SARS-CoV, SARS-CoV-2, and MERS-CoV. [00739] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by any of the alpha human coronaviruses. [00740] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by the alpha human coronaviruses 229E and NL63. [00741] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by any of the beta human coronaviruses. [00742] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by the beta human coronaviruses OC43, HKU1, SARS-CoV, SARS- CoV-2, and MERS-CoV. [00743] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by the human coronavirus SARS-CoV-2. [00744] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by the human coronavirus MERS-CoV. [00745] In other embodiments, the compounds described herein are useful for treating infections in a subject wherein the infection is caused by the human coronavirus SARS-CoV. [00746] In further embodiments, the compound of the present invention, or a pharmaceutically acceptable salt thereof, is chosen from the compounds set forth in Table 2. Phylogenetic Analysis [00747] The NCBI Virus sequence database for SARS-CoV-2 (taxid: 2697049; up to April 26, 2020) was reviewed for 3CLprotease (“3CLpro”) sequences. 108 protein sequences that were 306 amino acids in length were identified as 3CLpro sequences. The identified 3CLpro sequences were 100% identical to each other, and 100% identical to the amino acid sequence of the crystallized apo main protease (Zhang et al., Science 2020; PDB ID: 6Y2E). This consensus amino acid sequence was taken as the canonical 3CLpro- WT sequence. [00748] Varience of SARS-CoV-2 3Clpro was found in the longer ORF1a sequences (i.e., beyond those annotated to be 3CLpro). 1273 SARS-CoV-2 ORF1a sequences were analyzed for presence of 3CLpro, and their 3CLpro regions excised. 7 sequences were excluded for containing incomplete sequencing information in the 3CLpro region. Of the remaining 1266 sequences, 1222 were 100% identical to 3CLpro-WT (96.5% of sequences), and 44 featured mutations (3.5% of sequences) as shown in FIGs 1A- 1B. QIAX13818 and QJC42236 have two mutations each, A191V and L220F. [00749] In some embodiments, the coronavirus 3CL protease described herein is a mutant 3CL protease found in FIGs 1A-1B. Accordingly, provided compounds are degraders and/or inhibitors of mutant coronavirus 3CL protease and are therefore useful for treating one or more disorders associated with activity of a mutant coronavirus infection. Thus, in certain embodiments, the present invention provides a method for treating a mutant coronavirus-mediated disorder comprising the step of administering to a patient in need thereof a compound of the present invention, or pharmaceutically acceptable composition. Combination Therapies [00750] Depending upon the particular condition, or disease, to be treated, additional therapeutic agents, which are normally administered to treat that condition, may be administered in combination with compounds and compositions of this invention. As used herein, additional therapeutic agents that are normally administered to treat a particular disease, or condition, are known as “appropriate for the disease, or condition, being treated.” [00751] In certain embodiments, a provided combination, or composition thereof, is administered in combination with another therapeutic agent. [00752] In some embodiments, the present invention provides a method of treating a disclosed disease or condition comprising administering to a patient in need thereof an effective amount of a compound disclosed herein or a pharmaceutically acceptable salt thereof and co-administering simultaneously or sequentially an effective amount of one or more additional therapeutic agents, such as those described herein. In some embodiments, the method includes co-administering one additional therapeutic agent. In some embodiments, the method includes co-administering two additional therapeutic agents. In some embodiments, the combination of the disclosed compound and the additional therapeutic agent or agents acts synergistically. [00753] Those additional agents may be administered separately from a provided combination therapy, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as part of a multiple dosage regime, the two active agents may be submitted simultaneously, sequentially or within a period of time from one another normally within five hours from one another. [00754] As used herein, the term “combination,” “combined,” and related terms refers to the simultaneous or sequential administration of therapeutic agents in accordance with this invention. For example, a compound of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present invention provides a single unit dosage form comprising a compound of the current invention, an additional therapeutic agent, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. [00755] The amount of additional therapeutic agent present in the compositions of this invention will be no more than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. Preferably the amount of additional therapeutic agent in the presently disclosed compositions will range from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent. [00756] One or more other therapeutic agent may be administered separately from a compound or composition of the invention, as part of a multiple dosage regimen. Alternatively, one or more other therapeutic agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as a multiple dosage regime, one or more other therapeutic agent and a compound or composition of the invention may be administered simultaneously, sequentially or within a period of time from one another, for example within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 18, 20, 21, 22, 23, or 24 hours from one another. In some embodiments, one or more other therapeutic agent and a compound or composition of the invention are administered as a multiple dosage regimen within greater than 24 hours apart. [00757] In one embodiment, the present invention provides a composition comprising a provided compound and one or more additional therapeutic agents. The therapeutic agent may be administered together with a provided compound, or may be administered prior to or following administration of a provided compound. Suitable therapeutic agents are described in further detail below. In certain embodiments, a provided compound may be administered up to 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5, hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, or 18 hours before the therapeutic agent. In other embodiments, a provided compound may be administered up to 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5, hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, or 18 hours following the therapeutic agent. [00758] Depending upon the particular condition, or disease, to be treated, additional therapeutic agents that are normally administered to treat that condition, may also be present in the compositions of this invention. As used herein, additional therapeutic agents that are normally administered to treat a particular disease, or condition, are known as “appropriate for the disease, or condition, being treated.” [00759] A compound of the current invention can be administered alone or in combination with one or more other therapeutic compounds, possible combination therapy taking the form of fixed combinations or the administration of a compound of the invention and one or more other therapeutic compounds being staggered or given independently of one another, or the combined administration of fixed combinations and one or more other therapeutic compounds. Long-term therapy is equally possible as is adjuvant therapy in the context of other treatment strategies, as described above. [00760] Those additional agents may be administered separately from an inventive compound- containing composition, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as part of a multiple dosage regime, the two active agents may be submitted simultaneously, sequentially or within a period of time from one another normally within five hours from one another. [00761] The amount of both an inventive compound and additional therapeutic agent (in those compositions which comprise an additional therapeutic agent as described above) that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. Preferably, compositions of this invention should be formulated so that a dosage of between 0.01 - 100 mg/kg body weight/day of an inventive compound can be administered. [00762] In those compositions which comprise an additional therapeutic agent, that additional therapeutic agent and the compound of this invention may act synergistically. Therefore, the amount of additional therapeutic agent in such compositions will be less than that required in a monotherapy utilizing only that therapeutic agent. In such compositions a dosage of between 0.01 – 1,000 ^g/kg body weight/day of the additional therapeutic agent can be administered. [00763] The amount of one or more other therapeutic agent present in the compositions of this invention may be no more than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. Preferably the amount of one or more other therapeutic agent in the presently disclosed compositions will range from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent. In some embodiments, one or more other therapeutic agent is administered at a dosage of about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% of the amount normally administered for that agent. As used herein, the phrase “normally administered” means the amount an FDA approved therapeutic agent is provided for dosing per the FDA label insert. [00764] In certain embodiments, a provided compound is administered to a healthy or virus-infected patient, either as a single agent or in combination with (a) another agent that is effective in treating or preventing a coronavirus infection, (b) another agent that improves immune response and robustness, or (c) another agent that reduces inflammation and/or pain. [00765] In other embodiments, the compounds of the present invention may be used in combination with one or more antiviral therapeutic agents or anti-inflammatory agents useful in the prevention or treatment of viral diseases or associated pathophysiology. Thus, a provided compounds or a pharmaceutically acceptable derivatives thereof, may be employed alone or in combination with other antiviral or anti-inflammatory therapeutic agents. A provided compound or a pharmaceutically acceptable salts thereof may be used in combination with one or more other agents which may be useful in the prevention or treatment of respiratory disease, inflammatory disease, autoimmune disease, for example; anti-histamines, corticosteroids, (e.g., fluticasone propionate, fluticasone furoate, beclomethasone dipropionate, budesonide, ciclesonide, mometasone furoate, triamcinolone, flunisolide), NSAIDs, leukotriene modulators (e.g., montelukast, zafirlukast.pranlukast), tryptase inhibitors, IKK2 inhibitors, p38 inhibitors, Syk inhibitors, protease inhibitors such as elastase inhibitors, integrin antagonists (e.g., beta-2 integrin antagonists), adenosine A2a agonists, mediator release inhibitors such as sodium chromoglycate, 5-lipoxygenase inhibitors (zyflo), DP1 antagonists, DP2 antagonists, PI3K delta inhibitors, ITK inhibitors, LP (lysophosphatidic) inhibitors or FLAP (5-lipoxygenase activating protein) inhibitors (e.g., sodium 3-(3- (tert-butylthio)-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-((5-ethylpyridin-2-yl)methoxy)-1H-indol-2-yl)-2,2- dimethylpropanoate), bronchodilators (e.g..muscarinic antagonists, beta-2 agonists), methotrexate, and similar agents; monoclonal antibody therapy such as anti-lgE, anti- TNF, anti-IL-5, anti-IL-6, anti-IL-12, anti-IL-1 and similar agents; cytokine receptor therapies e.g. etanercept and similar agents; antigen non- specific immunotherapies (e.g., interferon or other cytokines/chemokines, chemokine receptor modulators such as CCR3, CCR4 or CXCR2 antagonists, other cytokine/chemokine agonists or antagonists, TLR agonists and similar agents), suitable anti-infective agents including antibiotic agents, antifungal agents, anthelmintic agents, antimalarial agents, antiprotozoal agents, antituberculosis agents, and antiviral agents. [00766] In some embodiments, a provided compound or a pharmaceutically acceptable salt thereof is administered in combination with an anti-infective agent selected from amebicides, aminoglycosides, anthelmintics, antifungals (e.g., azole antifungals, echinocandins, griseofulvin, terbinafine, flucytosine, polyenes), antimalarial agents (e.g., isoniazid/rifampin, isoniazid/pyrazinamide/rifampin, antimalarial quinolines, doxycycline, pyrimethamine, halofantrine), antituberculosis agents (e.g., aminosalicylates, antituberculosis combinations, diarylquinolines, hydrazide derivatives, ethambutol, nicotinic acid derivatives, rifamycin derivatives, streptomyces derivatives), antiviral agents (e.g., adamantane antivirals, antiviral boosters, antiviral combinations, antiviral interferons, chemokine receptor antagonist, integrase strand transfer inhibitor, fomivirsen, sofosbuvir, baloxavir barboxil, enfuvirtide, foscarnet, letermovir, ibalizumab, neuraminidase inhibitors, NNRTIs, NS5A inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors, purine nucleosides), carbapenems, carbapenems/beta-lactamase inhibitors, cephalosporins (e.g., cephalosporins/beta-lactamase inhibitors, first generation cephalosporins, fourth generation cephalosporins, next generation cephalosporins, second generation cephalosporins, third generation cephalosporins, glycopeptide antibiotics, glycylcyclines, leprostatics, lincomycin derivatives, macrolide derivatives (e.g., ketolides, macrolides), miscellaneous antibiotics (e.g., aztreonam, daptomycin, lefamulin, metronidazole, rifaximin, secnidazole, fosfomycin, chloramphenicol, atovaquone, aztreonam, bacitracin, colistimethate, erythromycin/sulfisoxazole, pentamidine, trimetrexate, spectinomycin), oxazolidinone antibiotics, penicillins (e.g., aminopenicillins, antipseudomonal penicillins, beta-lactamase inhibitors, natural penicillins, penicillinase resistant penicillins), quinolones, streptogramins, sulfonamides, tetracyclines, and urinary anti-infectives. [00767] In some embodiments, a provided compound or a pharmaceutically acceptable salt thereof is administered in combination with one or more of baricitinib, bevacizumab, chloroquine, colchicine, EIDD- 2801, favipiravir, fingolimod, hydroxychloroquine, azithromycin, ivermectin, leronlimab, lopinavir, ritonavir, oseltamivir, methylprednisolone, remdesivir, sarilumab, tocilizumab, umifenovir, avapritinib, and dapagliflozin. [00768] In some embodiments, the present invention provides a method of treating a coronavirus infection, the method comprising administering a provided compound or a pharmaceutically acceptable salt thereof in combination with one or more of baricitinib, bevacizumab, chloroquine, colchicine, EIDD-2801, favipiravir, fingolimod, hydroxychloroquine, azithromycin, ivermectin, leronlimab, lopinavir, ritonavir, oseltamivir, methylprednisolone, remdesivir, sarilumab, tocilizumab, umifenovir, avapritinib, and dapagliflozin. [00769] In some embodiments, the present invention provides a method as described comprising administering an additional agent selected from an antiviral agent, an antibiotic, an analgesic, a non- steroidal anti-inflammatory (NSAID) agent, an antifungal agent, an antiparasitic agent, an anti-nausea agent, an anti-diarrheal agent, or an immunosuppressant agent. In certain embodiments, the antiviral agent is an anti-hepatitis A agent or an antiretroviral agent. [00770] Suitably, for the treatment of asthma, a provided compound or pharmaceutical acceptable salt thereof may be administered together with an anti-inflammatory agent such as, for example, a corticosteroid, or a pharmaceutical formulation thereof. For example, a provided compound may be formulated together with an anti-inflammatory agent, such as a corticosteroid , in a single formulation, such as a dry powder formulation for inhalation. Alternatively, a pharmaceutical formulation comprising a provided compound may be administered in conjunction with a pharmaceutical formulation comprising an anti-inflammatory agent, such as a corticosteroid, either simultaneously or sequentially. In one embodiment, a pharmaceutical formulation comprising a provided compound and a pharmaceutical formulation comprising an anti-inflammatory agent, such as a corticosteroid, may each be held in device suitable for the simultaneous administration of both formulations via inhalation. [00771] Suitable corticosteroids for administration together with a provided compound include, but are not limited to, fluticasone furoate, fluticasone propionate, beclomethasone diproprionate, budesonide, ciclesonide, mometasone furoate, triamcinolone, flunisolide and prednisolone. In one embodiment, a provided compound is administered via inhalation with a corticosteroid including fluticasone furoate, fluticasone propionate, beclomethasone diproprionate, budesonide, ciclesonide, mometasone furoate, and flunisolide. [00772] Suitably, for the treatment of COPD, COPD-bronchiectasis overlap syndrome and bronchiectasis, compounds or pharmaceutical formulations of the invention may be administered together with one or more bronchodilators, or pharmaceutical formulations thereof. For example, a compound of the invention may be formulated together with one or more bronchodilators in a single formulation, such as a dry powder formulation for inhalation. Alternatively, a pharmaceutical formulation comprising a compound of the invention may be administered in conjunction with a pharmaceutical formulation comprising one or more bronchodilators, either simultaneously or sequentially. In a further alternative, a formulation comprising a compound of the invention and a bronchodilator may be administered in conjunction with a pharmaceutical formulation comprising a further bronchodilator. In one embodiment, a pharmaceutical formulation comprising a compound of the invention and a pharmaceutical formulation comprising one or more bronchodilators may each be held in device suitable for the simultaneous administration of both formulations via inhalation. In a further embodiment, a pharmaceutical formulation comprising a compound of the invention together with a bronchodilator and a pharmaceutical formulation comprising a further bronchodilator may each be held in one or more devices suitable for the simultaneous administration of both formulations via inhalation. [00773] Suitable bronchodilators for administration together with a compound of the invention include, but are not limited to, p2-adrenoreceptor agonists and anticholinergic agents. Examples of p2- adrenoreceptor agonists, include, for example, vilanterol, salmeterol, salbutamol, formoterol, salmefamol, fenoterol carmoterol, etanterol, naminterol, clenbuterol, pirbuterol, flerbuterol, reproterol, bambuterol, indacaterol, terbutaline and salts thereof, for example the xinafoate (1-hydroxy-2-naphthalenecarboxylate) salt of salmeterol, the sulphate salt of salbutamol or the fumarate salt of formoterol. Suitable anticholinergic agents include umeclidinium (for example, as the bromide), ipratropium (for example, as the bromide), oxitropium (for example, as the bromide) and tiotropium (for example, as the bromide). In one embodiment of the invention, a compound of the invention may be administered together with a p2-adrenoreceptor agonist, such as vilanterol, and an anticholinergic agent, such as umeclidinium. [00774] The compounds of the present invention and any other pharmaceutically active agent(s) may be administered together or separately and, when administered separately, administration may occur simultaneously or sequentially, in any order. The amounts of the compounds of the present invention and the other pharmaceutically active agent(s) and the relative timings of administration will be selected in order to achieve the desired combined therapeutic effect. The administration in combination of a compound of the present invention and salts, solvates, or other pharmaceutically acceptable derivatives thereof with other treatment agents may be in combination by administration concomitantly in: (1) a unitary pharmaceutical composition including both compounds; or (2) separate pharmaceutical compositions each including one of the compounds. In certain embodiments, the additional agent is administered as part of a single dosage form of said pharmaceutical formulation, or as a separate dosage form. [00775] Alternatively, the combination may be administered separately in a sequential manner wherein one treatment agent is administered first and the other second or vice versa. Such sequential administration may be close in time or remote in time. The amounts of a provided compound or a pharmaceutically acceptable salt thereof and the other pharmaceutically active agent(s) and the relative timings of administration will be selected in order to achieve the desired combined therapeutic effect. EXEMPLIFICATION Abbreviations Ac: acetyl AcOH: acetic acid ACN: acetonitrile Ad: adamantly AIBN: 2,2'-azo bisisobutyronitrile Anhyd: anhydrous Aq: aqueous B2Pin2: bis (pinacolato)diboron -4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) BINAP: 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl BH3: Borane Bn: benzyl Boc: tert-butoxycarbonyl Boc₂O: di-tert-butyl dicarbonate BPO: benzoyl peroxide nBuOH: n-butanol CDI: carbonyldiimidazole COD: cyclooctadiene d: days DABCO: 1,4-diazobicyclo[2.2.2]octane DAST: diethylaminosulfur trifluoride dba: dibenzylideneacetone DBU: 1,8-diazobicyclo[5.4.0]undec-7-ene DCE: 1,2-dichloroethane DCM: dichloromethane DEA: diethylamine DHP: dihydropyran DIBAL-H: diisobutylaluminum hydride DIPA: diisopropylamine DIPEA or DIEA: N,N-diisopropylethylamine DMA: N,N-dimethylacetamide DME: 1,2-dimethoxyethane DMAP: 4-dimethylaminopyridine DMF: N,N-dimethylformamide DMP: Dess-Martin periodinane DMSO-dimethyl sulfoxide DPPA: diphenylphosphoryl azide dppf: 1,1’-bis(diphenylphosphino)ferrocene EDC or EDCI: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride ee: enantiomeric excess ESI: electrospray ionization EA: ethyl acetate EtOAc: ethyl acetate EtOH: ethanol FA: formic acid h or hrs: hours HATU: N,N,N’,N’-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate HCl: hydrochloric acid HPLC: high performance liquid chromatography HOAc: acetic acid IBX: 2-iodoxybenzoic acid IPA: isopropyl alcohol KHMDS: potassium hexamethyldisilazide K₂CO₃: potassium carbonate LAH: lithium aluminum hydride LDA: lithium diisopropylamide m-CPBA: meta-chloroperbenzoic acid M: molar MeCN: acetonitrile MeOH: methanol Me₂S: dimethyl sulfide MeONa: sodium methylate MeI: iodomethane min: minutes mL: milliliters mM: millimolar mmol: millimoles MPa: mega pascal MOMCl: methyl chloromethyl ether MsCl: methanesulfonyl chloride MTBE: methyl tert-butyl ether nBuLi: n-butyllithium NaNO₂: sodium nitrite NaOH: sodium hydroxide Na2SO4: sodium sulfate NBS: N-bromosuccinimide NCS: N-chlorosuccinimide NFSI: N-Fluorobenzenesulfonimide NMO: N-methylmorpholine N-oxide NMP: N-methylpyrrolidine NMR: Nuclear Magnetic Resonance ^oC: degrees Celsius Pd/C: Palladium on Carbon Pd(OAc)₂: Palladium Acetate PBS: phosphate buffered saline PE: petroleum ether POCl₃: phosphorus oxychloride PPh₃: triphenylphosphine PyBOP: (Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate Rel: relative R.T. or rt: room temperature sat: saturated SEMCl: chloromethyl-2-trimethylsilylethyl ether SFC: supercritical fluid chromatography SOCl₂: sulfur dichloride tBuOK: potassium tert-butoxide TBAB: tetrabutylammonium bromide TBAI: tetrabutylammonium iodide TEA: triethylamine Tf: trifluoromethanesulfonate TfAA, TFMSA or Tf2O: trifluoromethanesulfonic anhydride TFA: trifluoracetic acid TIPS: triisopropylsilyl THF: tetrahydrofuran THP: tetrahydropyran TLC: thin layer chromatography TMEDA: tetramethylethylenediamine pTSA: para-toluenesulfonic acid wt: weight Xantphos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene General Synthetic Methods [00776] The following examples are intended to illustrate the invention and are not to be construed as being limitations thereon. Temperatures are given in degrees centigrade. If not mentioned otherwise, all evaporations are performed under reduced pressure, preferably between about 15 mm Hg and 100 mm Hg (= 20-133 mbar). The structure of final products, intermediates and starting materials is confirmed by standard analytical methods, e.g., microanalysis and spectroscopic characteristics, e.g., MS, IR, NMR. Abbreviations used are those conventional in the art. [00777] All starting materials, building blocks, reagents, acids, bases, dehydrating agents, solvents, and catalysts utilized to synthesis the compounds of the present invention are either commercially available or can be produced by organic synthesis methods known to one of ordinary skill in the art (Houben-Weyl 4th Ed. 1952, Methods of Organic Synthesis, Thieme, Volume 21). Further, the compounds of the present invention can be produced by organic synthesis methods known to one of ordinary skill in the art as shown in the following examples. [00778] All reactions are carried out under nitrogen or argon unless otherwise stated. [00779] Proton NMR (¹H NMR) is conducted in deuterated solvent. In certain compounds disclosed herein, one or more ¹H shifts overlap with residual proteo solvent signals; these signals have not been reported in the experimental provided hereinafter. Table 3: Analytical instruments

[00780] For acidic LCMS data: LCMS are recorded on an Agilent 1200 Series LC/MSD or Shimadzu LCMS2020 equipped with electro-spray ionization and quadruple MS detector [ES+ve to give MH⁺] and equipped with Chromolith Flash RP-18e 25*2.0 mm, eluting with 0.0375 vol% TFA in water (solvent A) and 0.01875 vol% TFA in acetonitrile (solvent B). Other LCMS is recorded on an Agilent 1290 Infinity RRLC attached with Agilent 6120 Mass detector. The column used is BEH C1850*2.1 mm, 1.7 micron. Column flow is 0.55 ml /min and mobile phase are used (A) 2 mM Ammonium Acetate in 0.1% Formic Acid in Water and (B) 0.1 % Formic Acid in Acetonitrile. [00781] For basic LCMS data: LCMS is recorded on an Agilent 1200 Series LC/MSD or Shimadzu LCMS 2020 equipped with electro-spray ionization and quadruple MS detector [ES+ve to give MH⁺] and equipped with Xbridge C18, 2.1X50 mm columns packed with 5 mm C18-coated silica or Kinetex EVO C182.1X30mm columns packed with 5 mm C18-coated silica, eluting with 0.05 vol% NH3·H2O in water (solvent A) and acetonitrile (solvent B). [00782] HPLC Analytical Method: HPLC is carried out on X Bridge C18 150*4.6 mm, 5 micron. Column flow is 1.0 ml /min and mobile phase are used (A) 0.1 % Ammonia in water and (B) 0.1 % Ammonia in Acetonitrile. [00783] Prep HPLC Analytical Method: The compounds are purified on Shimadzu LC-20AP and UV detector. The column used is X-BRIDGE C18 (250*19)mm, 5μ. Column flow is 16.0 ml/min. Mobile phase are used (A) 0.1% Formic Acid in Water and (B) Acetonitrile Basic method used (A) 5mM ammonium bicarbonate and 0.1% NH3 in Water and (B) Acetonitrile or (A) 0.1% Ammonium Hydroxide in Water and (B) Acetonitrile. The UV spectra are recorded at 202nm & 254nm. [00784] NMR Method: The 1H NMR spectra are recorded on a Bruker Ultra Shield Advance 400 MHz/5 mm Probe (BBFO). The chemical shifts are reported in part-per-million. [00785] As depicted in the Examples below, in certain exemplary embodiments, compounds are prepared according to the following general procedures. It will be appreciated that, although the general methods depict the synthesis of certain compounds of the present invention, the following general methods, and other methods known to one of ordinary skill in the art, can be applied to all compounds and subclasses and species of each of these compounds, as described herein. ****** [00786] While we have described a number of embodiments of this invention, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims rather than by the specific embodiments that have been represented by way of example.

Claims

CLAIMS We claim: 1. A compound of formula I:

I or a pharmaceutically acceptable salt thereof, wherein: PBM is a protease binding moiety capable of binding coronavirus protease; L is a bivalent moiety that connects PBM to DIM; and DIM is a degradation inducing moiety, such as a ligase binding moiety (LBM), lysine mimetic, or hydrogen atom. 2. The compound of claim 1, wherein said compound is a compound of formula I-aaa-1. I-aaa-2, I- aaa3, or I-aaa-4:

I-aaa-4 wherein:

z is 0, 1, 2, 3, or 4; Ring X is a ring selected from phenyl, a 5 to 7-membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5 to 9-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R^z is independently hydrogen, R^A, halogen, -CN, -NO₂, -OR, -SR, -N(R)₂, - Si(R)₃, -S(O)₂R, -S(O)₂N(R)_2, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or -N(R)S(O)₂R; R^x is hydrogen or R^A; and R^y is hydrogen, -OR, or R^A. 3. The compound of either claim 1 or claim 2, wherein LBM is a cereblon E3 ubiquitin ligase binding moiety, a VHL E3 ubiquitin ligase binding moiety, an IAP E3 ubiquitin ligase binding moiety, or an MDM2 E3 ubiquitin ligase binding moiety. 4. The compound of claim 3, wherein LBM is an cereblon E3 ubiquitin ligase binding moiety and said compound is of formula I-nn-1:

I-nn-1 or a pharmaceutically acceptable salt thereof, wherein: each of X¹, X², and X³ is independently a bivalent moiety selected from a covalent bond, –CH₂–, –C(O)–,

R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –NR2, or an optionally substituted C1-4 aliphatic; each of R² is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -NR2, -S(O)₂R, -S(O)₂NR2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or –N(R)S(O)₂R; Ring A is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7-membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; m is 0, 1, 2, 3 or 4; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4- 7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. 5. The compound of claim 4, wherein said compound is a compound of any of the following formulae:

I-aaa-11 or a pharmaceutically acceptable salt thereof. 6. The compound of claim 3, wherein LBM is a cereblon E3 ubiquitin ligase binding moiety and said compound is of formula I-a:

I-a or a pharmaceutically acceptable salt thereof, wherein: X¹ is a bivalent moiety selected from a covalent bond, –CH₂–, –CHCF3–, –SO₂–, –S(O)–, –P(O)R–, – P(O)OR–, –P(O)NR2–, –C(O)–, –C(S)–, or ; X² is a carbon atom or silicon atom; X³ is a bivalent moiety selected from –CR2–, –NR–, –O–, –S–, or –Si(R2)–; R¹ is hydrogen, deuterium, halogen, –CN, –OR, –SR, –S(O)R, –S(O)₂R, –N(R)₂, –P(O)(OR)₂, – P(O)(NR2)OR, –P(O)(NR2)₂, –Si(OH)₂R, –Si(OH)(R)₂, –Si(R)3, or an optionally substituted C1-4 aliphatic; each R² is independently hydrogen, deuterium, –R⁶, halogen, –CN, –NO₂, –OR, -SR, -N(R)₂, - Si(R)3, -S(O)₂R, -S(O)₂N(R)₂, -S(O)R, -C(O)R, -C(O)OR, –C(O)N(R)₂, -C(O)N(R)OR, - C(R)₂N(R)C(O)R, -C(R)₂N(R)C(O)N(R)₂, -OC(O)R, -OC(O)N(R)₂, -OP(O)R₂, -OP(O)(OR)₂, - OP(O)(OR)(NR₂), -OP(O)(NR₂)₂-, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)N(R)₂, –N(R)S(O)₂R, -NP(O)R₂, -N(R)P(O)(OR)₂, -N(R)P(O)(OR)(NR₂), -N(R)P(O)(NR₂)₂, or –N(R)S(O)₂R;

Ring B is a fused ring selected from 6-membered aryl, 6-membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5 to 7-membered saturated or partially unsaturated carbocyclyl, 5 to 7-membered saturated or partially unsaturated heterocyclyl ring with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5- membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; R³ is selected from hydrogen, halogen, –OR, –N(R)₂, or –SR; each R⁴ is independently hydrogen, –R⁶, halogen, –CN, –NO₂, –OR, - SR, -NR₂, -S(O)₂R, -S(O)₂NR_2, -S(O)R, -C(O)R, -C(O)OR, – C(O)NR₂, -C(O)N(R)OR, -OC(O)R, -OC(O)NR₂, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR₂, or –N(R)S(O)₂R; R⁵ is hydrogen, C1-4 aliphatic, or –CN; each R⁶ is independently an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L¹ is a covalent bond or a C1-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -O-, - C(O)-, -C(S)-, -C(R)₂-, -CH(R)-, -C(F)₂-, -N(R)-, -S(O)₂- or -(C)=CH-; m is 0, 1, 2, 3 or 4; each R is independently hydrogen, or an optionally substituted group selected from C_1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur. 7. The compound of claim 6, wherein said compound is a compound of any of the following formulae:

I-aaa-12

I-aaa-13 or pharmaceutically acceptable salt thereof. 8. The compound of claim 3, wherein LBM is a VHL E3 ubiquitin ligase binding moiety and said compound is selected from any of the following formulae: (i)

I-aa-2 or a pharmaceutically acceptable salt thereof, wherein each of the variables R¹, R², R³, X, and Y is as defined and described in WO 2019/084026; (ii)

I-aa-4 or a pharmaceutically acceptable salt thereof, wherein each of the variables R¹, R³, and Y is as defined and described in WO 2019/084030; (iii)

or a pharmaceutically acceptable salt thereof, wherein each of the variables R^1’, R^2’, R^3’, X, and X’ is as defined and described in WO 2013/106643 and US 2014/0356322; (

I-aa-14 I-aa-15 or a pharmaceutically acceptable salt thereof, wherein L and PBM are as defined above and described in embodiments herein, and wherein each of the variables R^1’, R^2’, R^3’, R5, R6, R7, R9, R10, R11, R14, R15, R16, R₁₇, R₂₃, R₂₅, E, G, M, X, X’, Y, Z₁, Z₂, Z₃, Z₄, and o is as defined and described in WO 2016/149668 and US 2016/0272639; and (v)

I-aa-17

I-aa-18 or a pharmaceutically acceptable salt thereof, wherein each of the variables R^p, R9, R10, R11, R14a, R14b, R15, R16, W³, W⁴, W⁵, X¹, X², and o is as defined and described in WO 2016/118666 and US 2016/0214972. 9. The compound according to claim 3 or claim 8, wherein the VHL E3 ubiquitin ligase binding

, ,

10. The compound of claim 3, wherein LBM is a IAP E3 ubiquitin ligase binding moiety and said compound is selected from any one of the following formulae: (i)

I-u-3

I-u-4 or a pharmaceutically acceptable salt thereof, wherein each of the variables R¹, R², R³, R⁴, R⁵, R⁶, and R⁷, is as defined and described in WO 2017/011590 and US 2007/037004; and (ii)

I-v or a pharmaceutically acceptable salt thereof, wherein each of the variables W, Y, Z, R¹, R², R³, R⁴, and R⁵ is as described and defined in WO 2014/044622, US 2015/0225449. WO 2015/071393, and US 2016/0272596. 11. The compound according to claim 3 or claim 10, wherein the IAP E3 ubiquitin ligase binding moiety is selected from

, ,

12. The compound of claim 3, wherein LBM is an MDM2 E3 ubiquitin ligase binding moiety and said compound is selected from any one of the following formulae: (i)

or a pharmaceutically acceptable salt thereof, wherein each of the variables R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, R₂₅, R₂₆, R₂₇, R₂₈, R_1’, R_2’, R_3’, R_4’, R_5’, R_6’, R_7’, R_8’, R_9’, R_10’, R_11’, R_12’, R_1’’, A, A’, A’’, X, Y, and Z is as defined and described in WO 2017/011371 and US 2017/008904; and (ii)

or a pharmaceutically acceptable salt thereof, wherein each of the variables R^12c, R^12d, R¹³, R¹⁷, R^18b, R^18c, R^18d, A⁵, A⁶, A⁷, Q¹, and Ar is as defined and described in WO 2017/176957 and US2019/127387. 13. The compound according to claim 3 or claim 12, wherein the MDM2 E3 ubiquitin ligase binding

. 14. The compound of any one of claims 1-13, wherein L is a covalent bond or a bivalent, saturated or partially unsaturated, straight or branched C_1-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -O-, -N(R)-, –Si(R)₂–, –Si(OH)(R)–, –Si(OH)₂–, –P(O)(OR)–, –P(O)(R)– , –P(O)(NR₂)–, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)₂-, -N(R)S(O)₂-, -S(O)₂N(R)-, -N(R)C(O)-, -

wherein: each –Cy– is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-11 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and; r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. 15. The compound of any one of claims 1-14, wherein said compound is selected from any one of the compounds depicted in Table 2, or a pharmaceutically acceptable salt thereof. 16. A pharmaceutical composition comprising a compound according to claim 15, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 17. The pharmaceutical composition according to claim 16, further comprising an additional therapeutic agent. 18. A method of inhibiting or degrading a coronavirus protease in a patient or biological sample comprising administering to said patient, or contacting said biological sample with a compound according to any one of claims 1-15, or a pharmaceutical composition thereof. 19. The method of claim 18, wherein the coronavirus protease is coronavirus 3CL protease. 20. A method of treating a coronavirus-mediated disorder, disease, or condition in a patient comprising administering to said patient a compound according to any one of claims 1-15, or a pharmaceutical composition thereof. 21. The method according to claim 20, further comprising administration of an additional therapeutic agent. 22. A method of treating a patient, the method comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-15, or a pharmaceutically acceptable salt thereof, wherein the patient has a coronavirus infection. 23. The methed of claim 22, wherein the coronavirus infection is SARS-CoV-2 infection.