STAT6 degraders and uses thereof

Abstract

The present disclosure relates generally to STAT 6 degraders and uses thereof, and more specifically to compounds, salts, and compositions thereof useful for treating conditions associated with STAT6.

Description

Attorney Docket No.: 18395-20370.40STAT6 DEGRADERS AND USES THEREOFCROSS REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims priority benefit to U. S. Provisional Application No.63 / 719,995, filed November 13, 2024, the disclosure of which is hereby incorporated herein by reference in its entirety for all purposes.FIELD

[0002] The present disclosure relates generally to STAT6 degraders and uses thereof, and more specifically to compounds, salts, and compositions thereof useful for treating conditions associated with STAT6.BACKGROUND

[0003] The Signal Transducer and Activator of 'Transcription (STAT) family of proteins consists of transcription factors that play an essential role m the regulation of cell processes, such as proliferation, differentiation, apoptosis and angiogenesis. Seven STAT genes have been identified in the human genome: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.

[0004] Recent studies have shown that STAT6 signaling is essential for IL-4- and IL- 13-induced epithelial mesenchymal transition (EMT) and aggressiveness of colorectal cancer cells (CRC) cells. STAT6 is involved in several aspects of inflammatory disease and other related conditions.

[0005] Given their role m the regulation of cell processes, modulating the activity of one or more STAT proteins, particularly STAT6, represent a pivotal area of investigation for the treatment of cancer, inflammatory conditions, and other therapeutic needs. Therefore, there is a substantial need to supply modulators of STAT, particularly STAT6 modulators.

[0006] Targeted protein degradation has become an advancing area as seen with rapid progression of PROTACs (proteolysis targeting chimeras) to clinic. PROTACs are protein degraders, which utilize the cell’s own waste disposal machinery to eliminate, instead of inhibit, a target protein. PROTACs are bifunctional in that they simultaneously bind a target protein and an E3 ligase protein. This event subsequently ubiquitylates the target, marking it1MF-363534227Attorney Docket No.: 18395-20370.40for proteasomal degradation. This, and related processes, represent a new therapeutic modality for the treatment of diseases.BRIEF SUMMARY

[0007] The present disclosure provides compounds of Formula (B), or a pharmaceutically acceptable salt thereof, compositions thereof, and methods of using these compounds, pharmaceutically acceptable salts thereof, and compositions thereof for the treatment of diseases or conditions associated with STAT, in particular STAT6.

[0008] In one aspect, provided is a compound of Formula (B),(B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: R101aand R101bare each independently H or halogen; R102is H, (Ci-C6)alkyl, or (C3-C6)cycloalkyl; R103is (Ci-Ce)alkyl, halo(Ci-Ce)alkyl, (C3-C&)cycloalkyl, 3- to 7-membered heterocyclyl, -(Ci-C6)alkylene-(C3- C6)cycloalkyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl of -(C]-C6)alkylene-(C3-C6)cycloalkyl, or (3- to 7-membered heterocyclyl) of -(Cj-C6)alkylene-(3- to 7-membered heterocyclyl) is each substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of (Ci-Ce)alkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Ci-C6)alkyl, and halo(Ci-C6)alkoxy, or R102and R103together with the nitrogen atom to which they are attached form 5- to 7-membered heterocyclyl substituted with 0, 1, 2, or 3 substituents each independently2MF-363534227Attorney Docket No.: 18395-20370.40selected from the group consisting of (Ci-C6)alkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Ci-C6)alkyl, and halo(Ci-C6)alkoxy, R104is H, (C6-Cio)aryl, or 5- to 10-membered heteroaryl, wherein (C6-Cio)aryl or 5- to 10-membered heteroaryl is each substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, (Ci-C6)alkyl, (Ci-Ce)alkoxy, halo(Ci-C6)alkyl, halo(Ci-C6)alkoxy, and -NR104aR104b, wherein: each R104aand R104bis independently H or (Ci-C6)alkyl; R105is H, cyano, or (Ci-C6)alkoxy; and Rpis phosphonic acid, phosphonate, phosphonamidate, or phosphondiamidate; L is aLbivalent moiety; and DIM is a degradation inducing moiety, whereinattached to a modifiable carbon, oxygen, or nitrogen atom.DETAILED DESCRIPTION

[0009] The following description is presented to enable a person of ordinary skill in the art to make and use the various embodiments. Descriptions of specific methods, techniques, and applications are provided only as examples. Various modifications to the examples described herein will be readily apparent to those of ordinary skill in the art, and the general principles defined herein may be applied to other examples and applications without departing from the spirit and scope of the various embodiments. Thus, the various embodiments are not intended to be limited to the examples described herein and shown, but are to be accorded the scope consistent with the claims.Definitions

[0010] As used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise.

[0011] Throughout this application, unless the context indicates otherwise, references to a compound of Formula (I) include all subgroups defined herein, such as Formula (I-A-l), (I-A-2), (I-A-3), (l-A-4), (I-A-5), (I-A-6), (I-B-l), (I-B-2), (I-B-3), (I-B-4), (I-B-5), (I-B-6), (I- C-l), (I-C-2), (I-C-3), (I-C-4), (I-C-5), (I-C-6), (I-D-l), (l-D-2), (I-D-3), (I-D-4), (I-D-5), (I- D-6), (I-E-l), (I-E-2), (I-E-3), (I-E-4), (I-E-5), (I-E-6), (I-F-l ), (I-F-2), (I-F-3), (I-F-4), (I-F-5), (I-F-6), (I-G-l), (I-G-2), (I-G-3), (I-G-4), (I-G-5), (I-G-6), (I-H-l), (I-H-2), (I-H-3), (I-H-4), (I-H-5), (I-H-6), (I-J-l), (I-J-2), (I-J-3), (I-J-4), (I-J-5), or (I-J-6) including all substructures, subgenera, preferences, embodiments, examples, and particular compounds 3MF-363534227Attorney Docket No.: 18395-20370.40defined and / or described herein. Throughout this application, unless the context indicates otherwise, references to a compound of Formula (B) include all subgroups defined herein, such as Formula (B-Rla), (B-Rlb), (B-RP), (B-R2), (B-R3), (B-R4), (B-R5), (B-RXa), or (B-VI), including all substructures, subgenera, preferences, embodiments, examples, and particular compounds defined and / or described herein. In some embodiments, references to a compound of Formula (I), Formula (A), Formula (B), and subgroups thereof include ionic forms, stereoisomers, rotamers, tautomers, oxides (e.g., N-oxides, S-oxides), esters, prodrugs, isotopologues, and / or protected forms thereof

[0012] When used in connection to describe a chemical group that may have multiple points of attachment, a hyphen (-) designates the point of attachment(s) of that group. For example, -NHC(O)OH means that the point of attachment for this group occurs on the nitrogen atom.

[0013] As used herein, “CX-CY” or “(Cx-Cy)” in reference to or preceding the name of a chemical group (e.g., alkyl, alkoxy, cycloalkyl, aryl) refers to the group having from X to Y carbon atoms, for example a (Cj-C6)alkyl refers to an alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms. The terms “halo” and “halogen” refer to an atom selected from fluorine (fluoro, -F), chlorine (chloro, -Cl), bromine (bromo, -Br), and iodine (iodo, -I).

[0014] Unless otherwise specified, the term “alkyl” when used alone or as part of a larger moiety, such as “haloalkyl”, and the like, means saturated straight-chain or branched monovalent hydrocarbon radical. For example, “(Ci-C6)alkyl” includes methyl, ethyl, propyl, isopropyl, n-butyl, 1 -methylpropyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, and hexyl. The term “alkylene” when used alone or as part of a larger moiety, such as “alkylenecycloalkyl”, and the like, means saturated straight-chain or branched divalent hydrocarbon radical, for example, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH(CH3)-, and - C(CH3)2-.

[0015] The term “haloalkyl” includes mono, poly, and perhaloalkyl groups where the halogens are independently selected from fluorine, chlorine, bromine, and iodine. In some embodiments, the halogen is fluorine. For example, haloalkyl includes chloromethyl, di chloromethyl, tnchloromethyl, fluoromethyl, difluoromethyl, tnfluoromethyl, 1,2-difluoroethyl, 2,2,2-trifluoroethyl, and 1,1,2,2-tetrafluoroethyl.4MF-363534227Attorney Docket No.: 18395-20370.40

[0016] “Alkoxy” means an alkyl radical attached through an oxygen linking atom, represented by -O-alkyl. For example, “(Ci-C4)alkoxy” includes methoxy, ethoxy, proproxy, and butoxy.

[0017] “Haloalkoxy” is a haloalkyl group which is attached to another moiety via an oxygen atom such as, e.g., -OCHF2 or -OCF3.

[0018] The term “oxo” means the group =0.

[0019] The term “imino” means the group::::NH.

[0020] Unless otherwise specified, the term “heteroaryl” refers to a 5- to 12-membered aromatic radical containing 1-4 heteroatoms selected from N, O, and S. In some instances, nitrogen atoms in a heteroaryl may be quaternized. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring”, “heteroaryl group”, or “heteroaromatic” A heteroaryl group may be mono- or bi-cychc. Monocyclic heteroaryl includes, for example, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, etc. Bi-cychc heteroaryls include groups in which a monocyclic heteroaryl ring is fused to one or more aryl or heteroaryl rings. Nonlimiting examples include indolyl, benzooxazolyl, benzooxodiazolyl, indazolyl, benzimidazolyl, benzthiazolyl, benzothiopheneyl, quinolinyl, quinazolinyl, quinoxalinyl, pyrrolopyridinyl, pyrrolopyrimidinyl, pyrrolopyndinyl, thienopyridinyl, thienopynmidinyl, indolizmyl, purinyl, cinnolinyl, naphthyridinyl, and ptendinyl. It will be understood that when specified, optional substituents on a heteroaryl group may be present on any substitutable position and, include, e.g., the position at which the heteroaryl is attached (where valency permits).

[0021] Unless otherwise specified, the term “heterocyclyl” means a 4- to 12-membered saturated or partial ly unsaturated heterocyclic ring containing 1 to 4 heteroatoms independently selected fromN, O, and S. The terms “heterocycle”, “heterocyclyl”, “heterocyclyl ring”, “heterocyclic group”, “heterocyclic moiety”, and “heterocyclic radical”, are used interchangeably herein. A heterocyclyl ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. A heterocyclyl group may be mono- or bicyclic (e.g., a bridged, fused, or spiro bicyclic ring). Examples of monocyclic saturated or partially unsaturated heterocyclic radicals include, without limitation, azetidmyl, tetrahydrofuranyl, tetrahydrothienyl, terahydropyranyl, pyrrolidinyl, pyrrolidonyl, pipendmyl, oxazolidinyl, piperazmyl, dioxanyl, dioxolanyl, morpholmyl, dihydrofuranyl.5MF-363534227Attorney Docket No.: 18395-20370.40dihydropyranyl, dihydropyndinyl, tetrahydropyndmyl, dihydropyrimidinyl, tetrahydropynmidinyl, dihydrooxadizolyl, and dihydroisoxazolyl, Bi-cyclic heterocyclyl groups include, e.g., unsaturated heterocyclic radicals fused to another unsaturated heterocyclic radical, cycloalkyl, aryl, or heteroaryl ring, such as for example, benzodioxolyl, dihydrobenzodioxinyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, 5-oxa-2,6-diazaspiro[3.4]oct-6-enyl, 6-thia-2,7-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.3]heptanyl, spiro[indoline-3,3'-pyrrolidine]-yl, thiochromanyl, and the like. It will be understood that when specified, optional substituents on a heterocyclyl group may be present on any substitutable position and, include, e.g., the position at which the heterocyclyl is attached (where valency permits).

[0022] The term “spiro” refers to two rings that shares one ring atom (e.g., carbon).

[0023] The term “fused” refers to two rings that share two adjacent ring atoms with one another.

[0024] The term “bridged” refers to two rings that share three adjacent ring atoms with one another.

[0025] The term “aryl” refers to an aromatic carbocyclic single ring or two fused ring system containing 6 to 10 carbon atoms. Examples include phenyl, mdanyl, tetrahydronaphthalene, and naphthyl. In one aspect, the aryl is phenyl or naphthyl. In some embodiments, the aryl is phenyl or naphthyl. In some embodiments, the aryl is phenyl.

[0026] The term “cycloalkyl”, used alone or as part of a larger moiety', refers to a saturated cyclic aliphatic monocyclic or bicyclic ring system, including spirocyclic ring system that may be referred to as “spirocycloalkyl”, having from, unless otherwise specified, 3 to 10 carbon ring atoms. Monocyclic cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, and cyclooctyl. It will be understood that when specified, optional substituents on a cycloalkyl or cycloaliphatic group may be present on any substitutable position and, include, e.g., the position at which the cycloalkyl group is attached.

[0027] The term “N-linked amino acid” refers to an amino acid that is attached to the indicated moiety via the main-chain amino group. For example, N-linked alanine can be represented by -NHCH(CH3)C(O)OH. N-linked amino acids can be substituted or unsubstituted.6MF-363534227Attorney Docket No.: 18395-20370.40

[0028] The term “N-lmked ammo acid ester” refers to an N-linked amino acid where the main-chain carboxylic acid group and / or any other carboxylic acid group(s) has been converted to an ester group. N-linked amino acid esters can be substituted or unsubstituted.

[0029] Fhe term “ammo acid” refers to any amino acid (both standard and non-standard amino acids, and both natural and non-natural amino acids), including, but not limited to, a-amino acids, [J-amino acids, y-amino acids, and 5-amino acids. Examples of suitable amino acids include, but are not limited to, alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Additional examples of suitable ammo acids include, but are not limited to, ornithine, hypusine, 2-ammoisobutync acid, dehydroalanine, gamma-aminobutyric acid, citrulline, beta-alanine, alpha-ethyl-glycine, alpha-propyl-glycine and norleucine.

[0030] Non-natural amino acids are known m the art and include, e.g., alpha-alkyl amino acids (e.g., alpha methyl), alpha-alkylalkoxy amino acids (e.g., alpha -CH2OCH3), N-methyl amino acids, homo-amino acids, etc.

[0031] The term “phosphonic acid,” as used herein, refers to an organophosphorous group containing a P(=O) moiety where the phosphorous atom is bonded to a carbon atom (herein the point of attachment of Rp) and two hydroxy groups, i.e., -P(=O)(OH)2. The term “phosphonate,” as used herein, refers to an organophosphorous group containing a P(::O) moiety where the phosphorous atom is bonded to a carbon atom (herein the point of attachment of Rp) and two monovalent oxy gen-linked groups, up to one of which may be hydroxy, and the other or both of which may be a non-hydroxy group, such as alkyloxy, aryloxy, cycloalkyloxy, heteroaryloxy, or heterocyclyloxy. The term “phosphonamidate,” as used herein, refers to an organophosphorous group containing a P(::O) moiety where the phosphorous atom is bonded to a carbon atom (herein the point of attachment of Rp), one monovalent oxygen-lmked group, such as hydroxy, alkyloxy, aryloxy, cycloalkyloxy, heteroarylox', or heterocyclyloxy, and one monovalent nitrogen-lmked group, such as alkylamino, arylammo, cycloalkylamino, heteroaryl ammo, heterocyclylammo, N-lmked amino acid, N-linked amino acid ester, N-linked heteroaryl, or N-linked heterocyclyl. The term “phosphondiamidate,” as used herein, refers to an organophosphorous group containing a P(=O) moiety where the phosphorous atom is bonded to a carbon atom (herein the point of attachment of Rp) and two monovalent nitrogen-lmked group, such as alkylamino, arylamino,7MF-363534227Attorney Docket No.: 18395-20370.40cycloalkylamino, heteroarylammo, heterocyclylammo, N-linked amino acid, N-lmked amino acid ester, N-lmked heteroaryl, or N-linked heterocyclyl.

[0032] The term ‘"substituted” refers to one or more hydrogen radical of the designated group being replaced with the radical(s) of a moiety other than hydrogen. Unless otherwise noted, the substituent! s) can be in any position(s), provided that the respective compound is sufficiently stable and pharmaceutically acceptable. Reference to a group being substituted by, for example, 0, 1, 2, or 3 substituents indicates the group is optionally substituted, that is the group may be unsubstituted (have zero substituents) or may be substituted with one, two, or three substituents.

[0033] Compounds having one or more chiral centers can exist in various stereoisomeric forms. Stereoisomers are compounds that differ only m their spatial arrangement.Stereoisomers include all diastereo enc, enantiomeric, and epimeric forms as well as racemates and mixtures thereof. A “geometric isomer” refers to stereoisomers that differ in the orientation of substituent group in relationship to a carbon-carbon double bond, a cycloalkyl ring, or a bridged bicyclic system. Atoms (other than H) on each side of a carboncarbon double bond may be in an E (substituents are on opposite sides of the carbon-carbon double bond) or Z (substituents are oriented on the same side) configuration. “Cis” refers to substituents oriented on the same side of a double bond or ring, whereas “trans” refers to substituents oriented on opposite sides of a double bond or ring.

[0034] When the stereochemical configuration at a chiral center in a compound having one or more chiral centers is depicted by its chemical name (e.g., where the configuration is indicated m the chemical name by “R” or “S”) or structure (e.g., the configuration is indicated by “wedge” bonds), the enrichment of the indicated configuration relative to the opposite configuration is greater than 50%, 60%, 70%, 80%, 90%, 99% or 99.9%.“Enrichment of the indicated configuration relative to the opposite configuration” is a mole percent and is determined by dividing the number of compounds with the indicated stereochemical configuration at the chiral center(s) by the total number of all of the compounds with the same or opposite stereochemical configuration in a mixture.

[0035] When a geometric isomer is depicted by name or structure, the enrichment of the indicated isomer relative to the opposite isomer is greater than 50%, 60%, 70%, 80%, 90%, 99% or 99.9%. “Enrichment of the indicated isomer relative to the opposite isomer” is a mole percent and is determined by dividing the number of compounds with the indicated8MF-363534227Attorney Docket No.: 18395-20370.40geometrical configuration by the total number of all of the compounds with the same or opposite geometrical configuration in a mixture.

[0036] When a disclosed compound is named or depicted by structure without indicating stereochemistry, it is understood that the name or the structure encompasses one of the possible stereoisomers or geometric isomers free of the others, or a mixture of the encompassed stereoisomers or geometric isomers.

[0037] The terms “subject” and “patient” may be used interchangeably, and means a mammal in need of treatment, e.g., companion animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, pigs, horses, sheep, goats and the like) and laboratory' animals (e.g., rats, mice, guinea pigs and the like). Typically, the subject is a human in need of treatment.

[0038] The term “inhibit,” “inhibition” or “inhibiting” includes a decrease in the baseline activity of a biological activity or process.

[0039] The term “pharmaceutical ly acceptable excipient” refers to a compound suitable for use in contact with recipient animals, particularly mammals, and more particularly humans, and having a toxicity, irritation, or allergic response commensurate with a reasonable benefit / risk ratio, and effective for their intended use.

[0040] As used herein, the term “pharmaceutically acceptable salt” refers to salts that are, within the scope of sound medical judgment, suitable for administration to a subject without undue toxicity, irritation, allergic response, or other undesired effect, commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts of the compounds descri be herein include those derived from suitable inorganic and organic acids and bases.

[0041] The term “effective amount” or “therapeutically effective amount” refers to an amount of a compound described herein that is sufficient to achieve the desired biological effect. In some embodiments, the effective amount is sufficient to achieve the desired therapeutic effect (such as treatment of a condition recited herein) under the conditions of administration by modulating, e.g., inhibiting STAT, in particular STAT6. The therapeutically effective amount will vary depending on the compound, the disease or condition and its severity and the age, weight, or other characteristics of the subject to be treated.

[0042] The term “administer,” “administering,” and “administration,” refer to contacting a subject with a compound or composition, or to prescribing, instructing, managing, or9MF-363534227Attorney Docket No.: 18395-20370.40supervising the contacting of a subject with a compound or a composition by the subject or by another.Compounds

[0043] Compounds and salts thereof (such as pharmaceutically acceptable salts) are detailed herein, including in the Brief Summary' and in the appended claims. Also provided are the use of al 1 of the compounds described herein, in cluding any and all stereoisomers, including geometric isomers (e.g., cis / trans, E / Z isomers), enantiomers, diastereomers, and mixtures thereof in any ratio including racemic mixtures, and salts of the compounds described herein, as well as methods of making such compounds. Any compound described herein may also be referred to as a drug.

[0044] In one aspect, provided is a compound of Formula (A):(A),or a pharmaceutically acceptable salt thereof, wherein SBM is a STAT6 binding moiety, L is a bivalent moiety that connects SBM to DIM, and DIM is a degradation inducing moiety. In some embodiments, the compound of Formula (A), or a pharmaceutically acceptable salt, is a(B), or a pharmaceutically acceptable salt, wherein SBM is a compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:10MF-363534227Attorney Docket No.: 18395-20370.40R101aand R101bare each independently H or halogen;R102is H, (Ci-C6)alkyl, or (C3-C6)cycloalkyl;R103is (Ci-Cejalkyl, halo(Ci-C6)alkyl, (C3-Ce)cycloalkyl, 3- to 7-membered heterocyclyl, -(Ci-C6)alkylene-(C3-C6)cycloalkyl, or -(Ci-C6)alkylene-(3- to 7- membered heterocyclyl), wherein (Ci-Ce)alkyl, (C3-C6)cycloalkyl, (C3- C6)cycloalkyl of -(Ci-C6)alkylene-(C3-C6)cycloalkyl, or (3- to 7-membered heterocyclyl) of -(Ci-C6)alkylene-(3- to 7 -membered heterocyclyl) is each substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of (Ci-Cejalkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Ci- C6)alkyl, and halo(Ci-C6)alkoxy,or R102and R103together with the nitrogen atom to which they are attached form 5- to 7-membered heterocyclyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of (Ci-C6)alkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Ci-C6)alkyl, and halo(Ci-Ce)alkoxy;R104is H, (C6-Cio)aryl, or 5- to 10-membered heteroaryl, wherein (C6-Cio)aryl or 5- to 10-membered heteroaryl is each substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, (Ci-C6)alkyl, (Ci-Ccdalkoxy, halo(Cj -Chalky!, halo(Ci-C6)alkoxy, and -NR104aR104b, wherein:each R104aand R104bis independently H or (Ci-Cbjalkyl;R105is H, cyano, or (Ci-C6)alkoxy; andRpis phosphonic acid, phosphonate, phosphonamidate, or phosphondiamidate;L is a bivalent moiety, andDIM is a degradation inducing moiety,L - ( DIM )wherein1Sattached to a modifiable carbon, oxygen, or nitrogen atom.

[0045] It will be understood that when a formula is depicted using square brackets with a dangling bond of a substituent extending across one of the brackets, the compound drawn inside the brackets is substituted with the substituent, or the substituent is attached to a modifiable carbon, oxygen, or nitrogen atom of the compound drawn inside the bracket. For11MF-363534227Attorney Docket No.: 18395-20370.40indicates that SBM is substituted with -L-DIM, or - L-DIM is attached to a modifiable carbon, oxygen, or nitrogen atom within SBM. It will be further understood that any reference to SBM herein can be a compound of Formula (I) or any subgroup defined herein, such as Formula (LA-1), (I-A-2), (I-A-3), (I-A-4), (LA-5), (I-A-6), (I-B-l), (I-B-2), (I-B-3), (I-B-4), (I-B-5), (l-B-6), (LC-1), (LC-2), (LC-3), (I-C-4), (L C-5), (I-C-6), (I-D-l), (I-D-2), (I-D-3), (I-D-4), (I-D-5), (I-D-6), (I-E-l), (I-E-2), (I-E-3), (I-E-4), (I-E-5), (I-E-6), (I-F-l), (I-F-2), (I-F-3), (I-F-4), (I-F-5), (I-F-6), (I-G-l), (LG-2), (I-G- 3), (LG-4), (LG-5), (LG-6), (I-H-l), (I-H-2), (I-H-3), (I-H-4), (I-H-5), (I-H-6), (I-J-l), (I-J-2), (LL3), (I-J-4), (I-J-5), or (I-J-6) including all substructures, subgenera, preferences, embodiments, examples, and particular compounds defined and / or described herein, or a monovalent form of any of such compounds, or a pharmaceutically acceptable salt thereof, depending on the context. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is selected from the group consisting of the compounds of Table 1A, Table IB, Table 1C, and pharmaceutically acceptable salts thereof. See Example 1.

[0046] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (LA- 1), (I-A-2), (I-A-3), (I-A-4), (LA-5), or (LA-6), or a pharmaceutically acceptable salt thereof:12MF-363534227Attorney Docket No.: 18395-20370.40

[0047] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-B-l), (I-B-2), (I-B-3), (I-B-4), (I-B-5), or (I-B-6), or a pharmaceutically acceptable salt thereof:13MF-363534227Attorney Docket No.: 18395-20370.4014MF-363534227Attorney Docket No.: 18395-20370.40wherein RPaa2is H or (Ci-Ce alkyl; and RPaa3is H. (Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C -Cejcycloalkyl.

[0048] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-C-l ), (I-C-2), (I-C-3), (I-C-4), (I-C-5), or (I-C-6), or a pharmaceutically acceptable salt thereof:15MF-363534227Attorney Docket No.: 18395-20370.40wherein RPais (Ci-Cyjalkyl, halo(Ci-Ce)alkyl, (C6-Cio)aryl, or (Cs-CQcycloalkyl, wherein (Ci-C6)alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-Cejalkoxy; RPaa2is H or (Ci-C6)alkyl; RPaa3is H, (Ci-Cz6)alkyl, -(Ci-C6)alkylene-(Cj-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; and RPaa4is (Ci-C6)alky 1, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, -(Ci-C6)alkylene-(C6-Cio)aryl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Cl-(36)alkyl, (C3-C6)cycloalkyl, (Cj-C8)spirocycloalkyl, or (C3-C-)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

[0049] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-D-l), (I-D-2), (I-D-3), (I-D-4), (I-D-5), or (I-D-6), or a pharmaceutically acceptable salt thereof, prior to its attachment to L:16MF-363534227Attorney Docket No.: 18395-20370.4017MF-363534227Attorney Docket No.: 18395-20370.40wherein each RPaa2is independently H or (Ci-C6)alkyl; and each RPaa3is independently I L (Ci-C6)alkyl, -(Ci-Cz6)alkylene-(Cj-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl.

[0050] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-E- l), (I-E-2), (I-E-3), (I-E-4), (I-E-5), or (I-E-6), or a pharmaceutically acceptable salt thereof:18MF-363534227Attorney Docket No.: 18395-20370.40pl 03N"(CH2)O-ICH3ozuRPaa4wherein RPaa2is H or (Ci-C6)alkyl; RPaa3is H, (Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; and RPaa4is (Ci-C6)alkyl, halo(Ci-C6)alkyl, -(C6- C6)alkylene-(Ci-C6)alkoxy, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, -(Ci-C6)alkylene-(C6-C10)aryl, -((Zj-Ce^alkylene-fCi-Celalkoxy, -(C;-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (C;-C6)alkyl, (C3-C6)cycloalkyl, (Cs-Cs)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

[0051] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-F-l), (I-F-2), (I-F-3), (I-F-4), (I-F-5), or (I-F-6), or a pharmaceutically acceptable salt thereof:19MF-363534227Attorney Docket No.: 18395-20370.40wherein RPaa2is H or (Ci-C6)alkyl; RPaa3is H, (Ci-C6)alkyl, -(Czi-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which. HOthey are attached form (C3-C6)cycloalkyl; and Ring A is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and -C(O)ORPEand eachRPEis independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, -(C;-C6)alkylene-(Ci-Cz6)alkoxy, (C3-C6)cycloalkyl, (C5-C3)spirocycloalkyl, -(CAC6)alkylene-(C6-Cio)aryl, -(€]- Cz6)alkylene-(C!-C3)alkoxy, -(Ci-C6)alkylene-(C3-Cz7)cycloalkyl, 3- to 7 -membered heterocyclyl, or -(Ci-Cs alkylene-Q- to 7-membered heterocyclyl), wherein (Cl-Cz6)alkyl, (C3-C6)cycloalkyl, (C5-Cs)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.20MF-363534227Attorney Docket No.: 18395-20370.40

[0052] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-G-l), (I-G-2), (I-G-3), (I-G-4), (I-G-5), or (I-G-6), or a pharmaceutically acceptable salt thereof:21MF-363534227Attorney Docket No.: 18395-20370.40wherein RPaa2is H or (Ci-Ce alkyl; RPaa3is H, (Ci-Cejalkyl, -(Ci-C6)alkylene-(Ci-Ce)alkoxy, or -(Ci-Cz6)alkylene-(Cz6-Cio)arjd; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; RPaa4is (Cl-C6)alkyl, halo(C;-C6)alkyl, -(C,- C6)alkylene-(C;-C6)alkoxy, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, -(C1-C6)alkylene-(C6-Cio)aryl. -(CyC6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7 -membered heterocyclyl), wherein (C>-C6)alkyl, (C3-C6)cycloalkyl, ((?z5-(?z8)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene- (Cz3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen; andRing A is HO substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and -C(O)ORPE; and each RPEis independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, -(Ci-C6)alkylene-(C Cio)aryl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-Cz6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (C C^alkyl, (CrCelcycloalkyl, (C5-C8)spirocycloalkyl, or (Cz3-C7)cycloalkyl of -(C;-C6)alkylene-(C3-Cz7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

[0053] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-H-l), (I-H-2), (I-H-3), (I-H-4), (l-H-5), or (I-H-6), or a pharmaceutical ly acceptable salt thereof:22MF-363534227Attorney Docket No.: 18395-20370.40wherein RP1and RP2are each independently -OH, -ORPa, -NRPaalCRPaa2RPaa3C(O)OH, -NRPaalCRPaa2RPaa3C(O)ORPaa4, or Ring A; RingA is ' substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and23MF-363534227Attorney Docket No.: 18395-20370.40-C(O)ORPE; RPais independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, (C6-Cio)aryl, or (C3-C6)cycloalkyl, wherein (Ci-Ccjalkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-Cejalkoxy, each RPEis independently (Ci-C6)alkyl, halo(Ci-Ce)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, (C3- C6)cycloalkyl, (C5-Cs)spirocycloalkyl, -(Ci-C6)alkylene-(C6-Cio)aryl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C?)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-Cz6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-CeOalkyl, (C3-C6)cycloalkyl, (C5-Cs)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen; each RPaalis independently H or (Ci-Cejalkyl; each RPaais independently H or (Ci-Cgjalkyl; each RPaa3is independently H, (Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; and each RPaa4is independently (Ci-C6)alky 1, halo(Ci-C6)alkyl, -(C1-C6)alkylene-(Ci-C6)alkoxy, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, -(Ci-C6)alkylene-(C6-C1S)aryl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

[0054] In some embodiments, R101aand R101bare each independently H or halogen. In some embodiments, R102is H, (Ci-Ce)alkyl, or (C3-C6)cycloalkyl. In some embodiments, R103is (Ci-C6)alkyl, halo(Ci-C6)alkyl, (C3-C6)cycloalkyl, 3- to 7-membered heterocyclyl, -(Ci-C>j)alkylene-(Ch-C6)cycloalkyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-Cz6)alkyl, (Cs-Celcycloalkyl, (C3-C6)cycloalkyl of -(Ci-Cz6)alkylene-(Cz3-C6)cycloalkyl, or (3- to 7-membered heterocyclyl) of -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl) is each substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of (Ci-Ce)alkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Ci-C6)alkyl, and halo(Ci-C6)alkoxy. In some embodiments, R10and R1L’3together with the nitrogen atom to which they are attached form 5- to 7-membered heterocyclyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of (Ci-C6)alkyl, (Ci-Cejalkoxy, cyano, halogen, halo(Ci-C6)alkyl, and halo(Ci-C6)alkoxy. In some embodiments, R1"4is H, (C6-Cio)aryl, or 5- to 10-membered heteroaryl, wherein (C6-Cio)aryl or 5- to 10-membered heteroaryl is each substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, (Ci-Cfjalkyl, (Ci-C6)alkoxy, halo(Ci-24MF-363534227Attorney Docket No.: 18395-20370.40Ce)alkyl, halofCi-Cejalkoxy, and -NR104aR104b, wherein: each R104aand R104bis independently H or (Ci-Cz6)alkyl. In some embodiments, R105is H, cyano, or (Ci-C6)alkoxy. In some embodiments, Rpis phosphonic acid, phosphonate, phosphonamidate, or phosphondiamidate.

[0055] In some embodiments, R101ais F, In some embodiments, R101bis H. In some embodiments, R101ais F and R101bis H. In some embodiments, R101aand R101bare each F.

[0056] In some embodiments, R102is methyl or ethyl.

[0057] In some embodiments, R103is (Ci-Celalkyl, halo(Ci-C6)alkyl, (C3-C6)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Cj-C6)alkylene-(3- to 7-membered heterocyclyl). In some embodiments, R103is halo(Ci-C6) alkyl. In some embodiments, R103is (C3- C6)cycloalkyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, halo(Ci-C6)alkyl, and halo(Ci-C6)alkoxy. In some embodiments, R10’ is 3-to 7-membered heterocyclyl. In some embodiments, R103is -(Cj-C6)alkylene-[3-to 7-membered heterocyclyl substituted with 0 or 1 (Ci-Csjalkyl], In some embodiments, R103is (Ci-Cejalkyl substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halo, (Ci-C6)alkoxy, and halo(Ci-C6)alkoxy. In some embodiments, R103is3'25MF-363534227Attorney Docket No.: 18395-20370.40

[0059] In some embodiments, R102and R103together with the nitrogen atom to which they are attached form 6-membered heterocyclyl.

[0060] In some embodiments,of Formula (I) is

[0061] In some embodiments, R104is H. In some embodiments, R104is (C6-Cio)aryl or 5-to 10-membered heteroaryl. In some embodiments, R104is phenyl substituted with 0, 1, 2, or3 halogen. In some embodiments, R104isIn some embodiments,R104is In some embodiments, R104is pyridmyl substituted with 0 or 1 -NR104aR104b. In someembodiments, R104isIn some embodiments, R104is

[0062] In some embodiments, R105is H. In some embodiments, R105is cyano. In some embodiments, R105is methoxy.

[0063] In some embodiments, DIM is a CRBN, VIIL, I AP, or MDM2 based E3 binder.26MF-363534227Attorney Docket No.: 18395-20370.40

[0064] In some embodiments, Rpis, wherein RP1and RP2are each independently -OH, -ORPa, N-linked amino acid, N-linked amino acid ester, or Ring A. Insome embodiments. Ring A is HNC ] substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and -C(O)ORPE. In some embodiments, RPais independently (Ci-Ccdalkyl, halo(Ci-C6)alkyl, (C6-Cio)aryl, or (C3-Cejcycloalkyl, wherein (Cj-Ce)alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-C6)alkoxy. In some embodiments, eachRPEis independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, -(C;-C6)alkylene-(C6-Cio)aryl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(C;-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7 -membered heterocyclyl, or -(C;-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-Ce^lkyl, (C3- C6)cycloalkyl, (C5-C8)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

[0065] In some embodiments, Rpis', wherein RP1and RP2are each independently -OH, -ORPa, -NRPaalCRPaa2RPaa3C(O)OH, -NRPaalCRPaa2RPaa3C(O)ORPaa4, orRing A. In some embodiments. RingA is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and -C(O)ORPE. In some embodiments, RPais independently (Ci-Cejalkyl, halo(Ci-C6)alkyl, (C6-Cio)aiyl, or (Ch-Ce cycloalkyl, wherein (Ci-C6)alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-C6)alkoxy. In some embodiments, eachRPEis independently (Ci -C6)alkyl, halo(Ci-C6)alkyl, -(Ci-Csjalkylene-(Ci-CQalkoxy, (C3-Ce)cycloalkyl, (Cs-Cslspirocycloalkyl, -(Ci-C6)alkylene-(C6-Cio)aryl, - (Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-Ce alkyl, (C3-C6)cycloalkyl, (Cs-Csjspirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-Cbjcycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen. In some embodiments, each RPaalis independently H or (Ci-Celalkyl. In some embodiments, each RPaa2is independently H or (Ci-Cejalkyl, and each RPaa3is independently H, (Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl, or RPaa2and RPaa3, together 27MF-363534227Attorney Docket No.: 18395-20370.40with the carbon atom to which they are attached form (C3-C6)cycloalkyl. In some embodiments, each RPaa4is independently (C C6)alkyl, halo(Ci-C«)alkyl, -(Ct-C«)alkylene-(Ci-C6)alkoxy, (Cs-Cs^ycloalkyl, (C3-C8)spirocycloalkyl, -(C!-C6)alkylene-(C6-Ci0)aiyd, -(C)-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C-)cycloaik}'i, 3- to 7 -membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (C3-C6)cycloalkyl, (Cj-Cs^pirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.RP1-P I =O

[0066] In some embodiments, RpisrP2, wherein RP1and RP2are each -OH.Rp1-P=O

[0067] In some embodiments, RpisrP2, wherein RP1is -OH and RPis N-Imked amino acid.•A / UVRP1_ ^QI

[0068] In some embodiments, RpisrP2, wherein RP1is -ORPaand RP2is N-linked amino acid ester. In some embodiments, RPais (Cj-C6)alkyl, halo(Ci-C6)alkyl, (C6-Cio)aryl, or (Cs-Cejcycloalkyl, wherein (Cj -C6)alkyl is substituted with 0, I, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-C6)alkoxy.Rp1-P=O

[0069] In some embodiments, RpisrP2, wherein RP1and RP2are eachwf WRp1-P=OIindependently N-linked amino acid. In some embodiments, RpisR, wherein RP1is -OH and RP2is N-linked amino acid ester.Rp1-P=OI

[0070] In some embodiments, RpisrP2, wherein RP1and RP2are each independently N-linked amino acid ester.28MF-363534227Attorney Docket No.: 18395-20370.40„-vRp1-P=O

[0071] In some embodiments, RpisrP2, wherein RP1is N-linked amino acid andP,..... H f"]R is Ring A, wherein Ring A is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and -COOH.Rp1-P=OI

[0072] In some embodiments, RpisrP2, wherein RP1is N-linked amino acid esterand RP2is Ring A, wherein Ring A issubstituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and ester.

[0073] In some embodiments, RPais phenyl. In some embodiments, RPais ethyl. In someembodiments, RPais -CH2CF3. In some embodiments, RPaiscyclopropyl, cyclopentyl, or cyclohexyl.Q HOOCsK, RN J N I

[0074] In some embodiments, R12is A-^ or1'w-J.J

[0075] In some embodiments, RP2is Ring A, wherein Ring A isA-> substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and -C(O)ORPEIn some embodiments, each RPEis independently (Ci-Ce alkyl, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, (Cs-Cc cycloalkyl, (Cs-Csjspirocycloalkyl, -(Ci-C6)alkylene-(C6-Cio)aiyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3- C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-Cr alkyl, (Cs-Csjcycloalkyl, (C5-Cs)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen. In some embodiments, each RPEis independently ethyl,29MF-363534227Attorney Docket No.: 18395-20370.40

[0077] In some embodiments, each N-linked amino acid is independently N-linked α-amino acid. In some embodiments, each N-linked amino acid ester is independently N-linked α-amino acid ester.

[0078] In some embodiments, each N-linked amino acid is independently - NRPaalCRPaa2RPaa3C(O)OH. In some embodiments, each N-linked amino acid ester is independently -NRPaalCRPaa2RPaa3C(O)ORPaa4.

[0079] In some embodiments, each RPaalis independently H or (Cj -C6)alky 1. In some embodiments, each RPaa2is independently H or (Ci-C6)alkyl, and each RPaa3is independently H, (Ci-Ce)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; orRPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl.

[0080] In some embodiments, RPaalis H. In some embodiments, RPaalis methyl.

[0081] In some embodiments, RPaa2is H. In some embodiments, RPaa2is methyl.

[0082] In some embodiments, RPaa3is methyl. In some embodiments, RPaa3is ethyl.I, or -CH2OCH3. In some embodiments, RPaa3is.

[0083] In some embodiments, RPaa2and RPaa3, together with the carbon atom to which they are attached form cyclopropyl.30MF-363534227Attorney Docket No.: 18395-20370.40

[0084] In some embodiments, each RPaa4is independently (Ci-Ce alkyl, halo(Ci-C6)alkyl, -(Ci -Chalky lene-(Ci-C6)alkoxy, (Cs-Celcycloalky 1, (C5-Cs)spirocycloalky 1, -(Ci-C6)alkylene-(C6-Cio)aryl, -(Ci-C6)alkydene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C?)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (C3-C6)cycloalkyl, (Cs-Csjspirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen. In some embodiments, each RPaa4is independently ethyl.

[0085] In some embodiments, the 4-azaspiro[2.4] heptane ring of Formula (I) covalently- attached to R104and R1(is substituted by -NHC(O)Rl0tDIM, -OR10CDIM, phenyl, (C3-Ce)cycloalkyl, 5- to 6-membered heteroaryl, or 4- to 6-membered heterocyclyl, wherein each of said phenyl, (C3-C6)cycloalkyl, 5- to 6-membered heteroaryl, and 4- to 6-membered heterocyclyl is substituted with -OR10CDIM, -NHR10CDIM, -[N(Ci-C4)alkyl]RlocDIM, or -R10CDIM, wherein said 4- to 6-membered heterocyclyl is optionally substituted further with oxo, and wherein R10Cis a chemical spacer unit.31MF-363534227Attorney Docket No.: 18395-20370.40

[0086] In some embodiments, R10Cis (Ci-Cio)alkylene or (C2-Cio)alkynelene, each of which is optionally substituted with one or more groups selected from the group consisting of halo and oxo, and wherein said (Cj-Cio)alkylene and (C2-Cio)alkynelene may also be optionally interrupted by one or more heteroatoms selected from the group consisting of S, N, and O, and / or optionally interrupted by one or more rings selected from the group consisting of 5- to 7-membered heteroaryl, (C3-C6)cycloakyl, phenyl, and 4- to 7-membered heterocyclyl,

[0087] In some embodiments, R10Cis (Ci-Cio)alkylene, (C2-Cio)alkynelene, - (CH2)tnC(O)NH[(CH2)O]v(CH2)n, -(CH2)O[(CH2)O]v(CH2)n, -(C2-C8)alkynelene[4- to 7-membered heterocyclyl], 4- to 7-membered heterocyclyl, [(CH2)O]v(CH2)n, or - (CH2)nC(O)NH[4- to 7-membered heterocyclyl], wherein m, n, and v are each independently 0, 1, 2, 3, 4, 5, or 6.to which DIM is attached.32MF-363534227Attorney Docket No.: 18395-20370.40is absent or C(O).

[0090] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-Rla),(B-Rla), or a pharmaceutically acceptable salt thereof.33MF-363534227Attorney Docket No.: 18395-20370.40

[0091] In some embodiments, the compound of Formula (B), or a pharmaceuticallyacceptable salt thereof, is a compound of FormulaRib), (B-Rlb), or a pharmaceutically acceptable salt thereof.

[0092] In some embodiments, the compound of Formula (B), or a pharmaceuticallyacceptable salt thereof, is a compound of Formula (B-RP), (B-RP), or a pharmaceutically acceptable salt thereof.

[0093] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-R2),Rp(B-R2), or a pharmaceutically acceptable salt thereof.34MF-363534227Attorney Docket No.: 18395-20370.40

[0094] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-R3),(B-R3), or a pharmaceutically acceptable salt thereof.

[0095] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-R4),(B-R4), or a pharmaceutically acceptable salt thereof.

[0096] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-R5),Rp(B-R5), or a pharmaceutically acceptable salt thereof.

[0097] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-RX),35MF-363534227Attorney Docket No.: 18395-20370.40^>103RxRp(B-RX), or a pharmaceutically acceptable saltthereof, wherein one Rxis and each remaining Rxis H.

[0098] In some embodiments, the compound of Formula (B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (B-RXa),(B-RXa), or a pharmaceutically acceptable salt thereof.

[0099] In some embodiments.is attached to a modifiable carbon,nitrogen, or oxygen atom of RpIn some embodiments,modifiable carbon, nitrogen, or oxygen atom of R102, In some embodiments.is attached to a modifiable carbon, nitrogen, or oxygen atom of R103. In some embodiments, R102and R103together with the nitrogen atom to which they are attached form 5- to 7 -membered heterocyclyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of (Ci-Ce)alkyl, (Cj-C6)alkoxy, cyano,36MF-363534227Attorney Docket No.: 18395-20370.40halogen, halo(Ci-C6)alkyl, and halo(Ci-C6)alkoxy, andmodifiable carbon, nitrogen, or oxygen atom of the 5- to 7-membered heterocyclyl or asubstituent thereof. In some embodiments,is attached to a modifiablecarbon, nitrogen, or oxygen atom of R104In some embodiments.attached to a modifiable carbon, nitrogen, or oxygen atom of R105.

[0100] In some embodiments, DIM is an E3 ubiquitin ligase binding moiety (LBM) selected from the group consisting of a cereblon E3 ubiquitin ligase binding moiety, a VHL E3 ubiquitin ligase binding moiety', an IAP E3 ubiquitin ligase binding moiety, and an MDM2 E3 ubiquitin ligase binding moiety. In some embodiments, the E3 ubiquitin ligase binding moiety (LBM) is a cereblon E3 ubiquitin ligase binding moiety. In some embodiments, the E3 ubiquitin ligase binding moiety (LBM) is a VHL E3 ubiquitin ligase binding moiety. In some embodiments, the E3 ubiquitin ligase binding moiety (LBM) is a LAP E3 ubiquitin ligase binding moiety. In some embodiments, the E3 ubiquitin ligase binding moiety (LBM) is an MDM2 E3 ubiquitin ligase binding moiety'.

[0101] In one aspect, provided herein is a parent drug. In some embodiments, a prodrug can be metabolized to produce the parent drug. In some embodiments, the prodrug can be metabolized to produce an intermediate metabolite. In some embodiments, the intermediate metabolite can be further metabolized to produce the parent drug. In some embodiments, the prodrug can be metabolized by enzymes such as carboxyesterase and / or phosphoramidase to produce the parent drug. In some embodiments, the prodrug is a ProTide prodrug analog (see, e.g., Mehellou, et al., J. Med. Chem. 61(6) 2211-2226 (2018). In some embodiments, the prodrug has an Rpselected from those present in molecules described herein m the representative procedures for synthesis of phosphoryl groups of Example 1.

[0102] In some embodiments, the parent drug is the compound of Formula (B),(B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (LA-1), (LA-2), (LA-3), (LA-4), (LA-5), or (LA-6), or a 37MF-363534227Attorney Docket No.: 18395-20370.40pharmaceutically acceptable salt thereof. In some embodiments, the parent drug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is aHo—Icompound of Formula (I), wherein Rpis, or a pharmaceutically acceptable salt thereof. In some embodiments, the parent drug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound selected from the group consisting of the compounds of Table I A, or a pharmaceutically acceptable salt thereof.

[0103] In some embodiments, SBM is selected from the group consisting of:(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4Jheptane-4-carbonyl)decahydropyrrolo[l,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4] heptane-4-carbony l)decahydropyrrol o[ 1,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)ammo)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphomc acid;((2-((3-(7-cyano-6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)-9-morpholino-5- oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;(fluoro(2-((9-morpholmo-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocm-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;((2-((3-(6-(4-(dimethylamino)pyridin-3-yl)-4-azaspiro[2.4]heptane-4-carbonyl)-9- morpholino-5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;(fluoro(2-((9-morpholino-5-oxo-3-(6-(pyndin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;38MF-363534227Attorney Docket No.: 18395-20370.40 (fluoro(2-((9-morpholmo-5-oxo-3-(6-(pyridm-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]az.ocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;((2-((3-(7-cyano-6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4-carbonyl)-9-morpholino-5- oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;((2-((3 -(6-(4-(dimethy lamin o)pyri din-3 -yl)-4-azaspiro[2.4] heptane-4-carbony l)-9- morpliolino-5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;(fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(oxetan-3-ylmethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4] heptane-4-carbony l)decahydropyrrol o[ 1,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- y 1 )methy l)phosphoni c aci d;(fluoro(2-((9-(methyl((oxetan-2-yl)methyl)ammo)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocm-6- yl)carbamoyl)benz.o[b]thiophen-5-yl)methyl)phosphonic acid;((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;2,2,2-trifluoroacetic acid compound with ((2-((9-((3,3-difluorocyclobutyd)(methyl)amino)- 5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;39MF-363534227Attorney Docket No.: 18395-20370.40 (fluoro(2-((9-(methyl((oxetan-2-yl)methyl)ammo)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;((2-((9-((3,3-difluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;(fl uoro(2-((9-(methy 1 ( tetrahy drofuran-3 -yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocm-6- yl)carbamoyl)benz.o[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((3-(6-(3-fluorophenyl)-4-azaspiro[2.4]heptane-4-carbonyl)-9-(methyl(oxetan-3- yl)amino)-5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4] heptane-4-carbony l)decahydropyrrol o[ 1,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid,(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-(pyridin-3-yl)-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid.;(fluoro(2-((9-(methyl((oxetan-2-yl)methyl)ammo)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(3-fluorocyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(3-fluorocyclobutyl)aniino)-5-oxo-3-(6-plienyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;((2-((9-((3-(difluoromethyl)cyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid,40MF-363534227Attorney Docket No.: 18395-20370.40 (fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)ammo)-5-oxo-3-(4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;2,2,2-trifluoroacetic acid compound with ((2-((9-(ethyl((3-methyloxetan-3- yl)methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(3-(trifluoromethoxy)cyclobuty])amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(4,4,4-tnfluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocm-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)phosphonic acid,((2-((9-(ethyl(3-(trifluoromethyl)cyc[obutyl)amino)-5-oxo-3-(6-pheny[-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;((2-((9-(ethyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;(fluoro(2-((9-(methyl((3-(trifluoromethyl)cyclobutyl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl((3-(trifluoromethyl)cyclobutyl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(2-(1-(trifluoromethyl)cyclopropyl)ethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4] heptane-4-carbony l)decahydropyrrol o[ 1,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;41MF-363534227Attorney Docket No.: 18395-20370.40 (fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphomc acid;(fluoro(2-((9-(methyl(3-(trifluoromethoxy)propyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(4,4,4-trifluoro-3-methoxybutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-morpholino-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)phosphonic acid;((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4] heptane-4-carbony l)decahydropyrrol o[ 1,2-a]azocm-6- yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphonic acid;(fluoro(2-((9-(methyl((3-methyloxetan-3-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclopentyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(difluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-(pyridin-3-yl)-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-(pyridin-3-yl)-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((3-(7-methoxy-6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)-9-(methyl(3- (tnfluoromethoxy)cyclobutyl)ammo)-5-oxodecahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((3-(7 -methoxy -6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)-9-(methyl(3- (trifluoromethoxy)cyclobutyl)amino)-5-oxodecahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(3,3,3-trifluoro-2-methoxypropyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid;(fluoro(2-((9-(methyl(2-(trifluoromethoxy)ethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid; and42MF-363534227Attorney Docket No.: 18395-20370.40(fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphonic acid,and pharmaceutically acceptable salts thereof.

[0104] In some embodiments, the prodrug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I),Rp1-P=Owherein RpisrP2, wherein RP1and RP2are each independently -ORPa, or a pharmaceutically acceptable salt thereof.

[0105] In some embodiments, the prodrug is the compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I-C-l), (I-C-2), (I-C-3), (I-C-4), (I-C-5), or (I-C-6), or a pharmaceutically acceptable salt thereof. In some embodiments, the prodrug is a compound of Formula (B), or a pharmaceuticallyRp1-P=O I acceptable salt thereof, wherein SBM is a compound of Formula (I), wherein RpisRwherein RP1is -ORPaand RP2is N-linked amino acid ester, or a pharmaceutically acceptable salt thereof. In some embodiments, the intermediate metabolite of the prodrug is the compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I-B-l), (I-B-2), (I-B-3), (I-B-4), (I-B-5), or (I-B-6), or a pharmaceutically acceptable salt thereof. In some embodiments, the intermediate metabolite of the prodrug is a compound of Formula (B ), or a pharmaceutically acceptable salt thereof,Rp1-P=Owherein SBM is a compound of Formula (I), wherein RpisR, wherein RP1is -OH and RP2is N-linked amino acid, or a pharmaceutically acceptable salt thereof. In someRp1-P=Oembodiments, SBM is a compound of formula (I), wherein RpisR, wherein RP1is - -NRPaa1CRPaa2RPaa3OH, and RP2is O OH insome embodiments, SBM is a compound of formula (I),43MF-363534227Attorney Docket No.: 18395-20370.40I HNX / RP' P--0 Iwherein RpisrP2, wherein RP1is -OH, and RP2is ® ORPaa4jnsomeRP1-P=OIembodiments, SBM is a compound of formula (I), wherein RpisrP2, wherein RP1is - sA / WVtAA.HN._xOH, and RP2is O^OH.

[0106] In some embodiments, the prodrug is the compound of Formula (B ), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I -E- 1 ), (I-E-2), (I-E-3), (I-E-4), (I-E-5), or (I-E-6), or a pharmaceutically acceptable salt thereof. In some embodiments, the prodrug is a compound of Formula (B), or a pharmaceuticallyRp1-P=O acceptable salt thereof, wherein SBM is a compound of Formula (I), wherein RpisrP2, wherein RP1and RP2are each independently N-linked amino acid ester, or a pharmaceutically acceptable salt thereof. In some embodiments, the intermediate metabolite of the prodrug is the compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I-D-l), (I-D-2), (I-D-3), (I-D-4), (I-D-5), or (I-D-6), or a pharmaceutically acceptable salt thereof. In some embodiments, the intermediate metabolite of the prodrug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, rfVWRp1-P i =Owherein SBM is a compound of Formula (I), wherein RpisrP“!, wherein RP1and RP2are each independently N-linked amino acid, or a pharmaceutically acceptable salt thereof.

[0107] In some embodiments, the prodrug is the compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I-G-l), (I-G-2), (I-G-3), (I-G-4), (I-G-5), or (I-G-6), or a pharmaceutically acceptable salt thereof, wherein Ring A is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and ester. In some embodiments, the prodrug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a »vwRp1-P! =Ocompound of Formula (I), wherein RpisrP2, wherein RP1is N-linked amino acid ester44MF-363534227Attorney Docket No.: 18395-20370.40and RP2is Ring A, wherein Ring A issubstituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and ester, or a pharmaceutically acceptable salt thereof. In some embodiments, the intermediate metabolite of the prodrug is the compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I-F-l ), (I-F-2), (I-F-3), (I-F-4), (I-F-5), or (I-F-6), or a pharmaceutically acceptable salt thereof, wherein Ring K is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and -COOH. In some embodiments, the intermediate metabolite of the prodrug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound of FormulaRP1-P I =O(I), wherein RpisrP2, wherein RPiis N-linked amino acid and RP2is Ring A, whereinRing A issubstituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and -COOH, or a pharmaceutically acceptable salt thereof.

[0108] In some embodiments, the prodrug is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound selected from the group consisting of the compounds of Table 1C, or a pharmaceutically acceptable salt thereof. In some embodiments, the intermedi ate metabolite is a compound of Formula (B), or a pharmaceutically acceptable salt thereof, wherein SBM is a compound selected from the group consisting of the compounds of Table IB, or a pharmaceutically acceptable salt thereof.

[0109] In some embodiments, SBM is a compound of formula (I), wherein RpisRP1P i =OR, wherein RP1is -OH, and RP2is N-linked amino acid ester. In some embodiments,Rp1~P I -0SBM is a compound of formula (I), wherein RpisR, wherein RP1is -Oi l, and RPis < / WVWWHN^_RRPaa3O ORPaa4in some embodiments, SBM is a compound of formula (I), wherein Rpis45MF-363534227Attorney Docket No.: 18395-20370.40HNRp1~P-0 TRP2, wherein RP1is -OH, and RP2is O ORPaa4jnsome embodiments, the SBM isRp1-P=Oa compound of formula (I), wherein Rpis RP2, wherein RP1is -OH, RP2isF, or O. In some embodiments, SBM is aHNRp1P=O compound of formula (I), wherein Rpis RP2, wherein RP1is -OH, RP2i ORPaa4and RPaa4i, orIn some embodiments, SBM is a compound of formula (I), wherein Rpis uvuvvwvvHN RP1P=ORp2wherein RP1is -OH, RP2is ° ORPaa4,anc| RPaa4is

[0110] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-J-l ), ( I - J-2 ), (I-J-3), (I-J-4), (I-J-5), or (I-J-6), or a pharmaceutically acceptable salt thereof46MF-363534227Attorney Docket No.: 18395-20370.4047MF-363534227Attorney Docket No.: 18395-20370.40

[0111] wherein RPaa2is H or (Ci-Cejalkyl; and RPaa3is H, (Ci-C6)alkyl, -(Ci-Cejalkylene-(Ci-CQalkoxy, or -(Cj-C6)alkylene-(C6-C]o)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; and RPaa4is (C1-C6)alkyl.

[0112] In some embodiments, SBM is selected from the group consisting of:((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (hy droxy )pho sphory 1) -al ani ne;((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -yl)m ethyl)(hydroxy)phosphoryl) -alanine;((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a|azocin-6-yl)carbamoyl)benzo|b]thiophen- 5 -yl)m ethyl)(hydroxy)phosphoryl) -alanine;((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a|azocin-6-yl)carbamoyl)benzo|b]thiophen- 5 -yl)m ethyl)(hydroxy)phosphoryl) -alanine;((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a ]azocin-6-yl)carbamoyl)benzo[b |thiophen-5 - yl)m ethyl) (hydroxy )pho sphory 1) -al am ne;(((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl) (hydroxy )phosphoryl ) -al anine;((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (hydroxy )pho sphory 1) -al am ne;(((2-((9-(ethyl(3-fluorocyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl) (hy droxy )phosphoryl) -alanine;((fluoro(2-((9-(methyl((3-methyloxetan-3-yl)niethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(hydroxy)phosphoryl)-alanine;(((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl) (hy droxy )phosphoryl) -alanine;(((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocm -6 -yl )carbam oyl)benzo [b]thi ophen -5 - yl)fluoromethyl) (hy droxy )phosphoryl) -alanine;((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)m ethyl) (hydroxy )pho sphoryl) -alanine;48MF-363534227Attorney Docket No.: 18395-20370.40((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(hydroxy)phosphoryl)-alanine;(((2-((9-(ethyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl) (hy droxy)phosphoryl) -alanine;(((2-((9-(ethyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocin -6 -yl )carbam oy l)benzo [bjthi ophen -5 - yl)fluoromethyl) (hy droxy)phosphoryl) -alanine;(((2-((9-((3-(difluoromethyl)cyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (hydroxy )pho sphoryl) -alanine;((fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (hydroxy )pho sphoryl) -alanine;((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-(methyl((oxetan-2-yl)niethyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4jheptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(hydroxy)phosphoryl)-alanine;((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(hydroxy)phosphoryl)-alanine;(((2-((9-(ethyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(hydroxy)phosphoryl)-alanine;(((2-((9-(ethyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(hydroxy)phosphoryl)-alanine; and((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)niethyl)(hydroxy)pbosphoryl)-alairine,49MF-363534227Attorney Docket No.: 18395-20370.40and pharmaceutically acceptable salts thereof.

[0113] In some embodiments, SBM is selected from the group consisting ofpropyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro|2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl) (phenoxy )pho sphoryl) -alaninate;propyl (((2-((9-((3,3-difluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3-dihydrobenzo[b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3-dihydrobenzo[b]thiophen-5- yl)fluoromethyl) (phenoxy)pho sphoryl) -alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4Jheptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro|2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3-dihydrobenzo[b]thiophen-5- yl)fluoromethyl) (phenoxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - y l)fl u oromethyl) (phen oxy)pho sphoryl) -alaninate;propyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;50MF-363534227Attorney Docket No.: 18395-20370.40propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;propyl ((fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1.2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yDmethyD(phenoxy)phosphoiyl)-alaninate;propyl ((fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2.4 ]heptane-4-carbonyl)decahy dropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl)-2,3 - dihydrobenzo [b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2.4]heptane-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin -6-yl)carbamoyl)-2,3 - dihydrobenzo [b ]thiophen-5 -yl)methyl) (phenoxy)phosphory 1) -alaninate;propyl ((fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate; propyl ((fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(oxetan-3-ylmethyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo| l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen-5- yl)m ethyl) (ph enoxy)pho sphoryl ) -al aninate;propyl ((fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-(pyridin-3-yl)-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocin -6 -yl )carbam oyl)benzo [bjthi ophen-5 - yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (ph enoxy)pho sphory 1 ) -al aninate;propyl (((2-((3-(6-(4-(dimethylamino)pyridin-3-yl)-4-azaspiro[2.4]heptane-4-carbonyl)-9- morpliolino-5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl) (phenoxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-(metliyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbanioyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocin -6 -yl )carbam oy l)benzo [b]thi ophen -5 - yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 -yl)m ethyl) (ph enoxy)pho sphoryl ) -al aninate;51MF-363534227Attorney Docket No.: 18395-20370.40propyl ((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2 -a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((3-(6-(3-fluorophenyl)-4-azaspiro[2.4]heptane-4-carbonyl)-9-(methyl(oxetan-3- yl)aniino)-5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbanioyl)benzo[b]thiophen-5 - yl)m ethyl) (phenoxy )pho sphoryl) -alaninate;propyl (((2-((3-(7-cyano-6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)-9-morpholino-5- oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocin -6 -yl )carbam oy l)benzo [bjthi ophen-5 - yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (phenoxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4jheptane-4- carbonyl)decahydropyrrolo[ 1,2-a |azocin-6-yl)carbamoyl)benzo[b |thiophen-5 - vl)m ethyl) (phen oxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocin -6 -yl )carbam oyl)benzo [bjthi ophen-5 - yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((3-(7-cyano-6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4-carbonyl)-9-morpholino-5- oxodecahy dropyrrolo [ 1,2-a] azocin-6-y l)carbamoyl)benzo [ b ] thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((3-(7-cyano-6-(pyridin-3-yl)-4-azaspiro[2.4|heptane-4-carbonyl)-9-morpholino-5- oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl) (phenoxy )pho sphoryl) -alaninate;propyl (((2-((3-(6-(4-(dimethylamino)pyridin-3-yl)-4-azaspiro[2.4]heptane-4-carbonyl)-9- morpholino-5-oxodecahydropyrrolo| l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((3-(6-(4-(dimethylamino)pyridin-3-yl)-4-azaspiro|2.4]heptane-4-carbonyl)-9- morpholino-.5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((3-(6-(4-(dimetbylamino)pyridin-3-yl)-4-azaspiro[2.4]heptane-4-carbonyl)-9- morpholino-5-oxodecahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b|thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;isopropyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (phenoxy )pho sphoryl) -alaninate;isopropyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-(pyridin-3-yl)-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - vl)m ethyl) (phen oxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-(methyl((oxetan-2-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;benzyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 -yl)fluoromethvl)(phenoxy)phosphoryl)-alaninate;52MF-363534227Attorney Docket No.: 18395-20370.40propyl 2-((((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2 -a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyD(phenoxy)phosphoryl)amino)butanoate;2 -methoxyethyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y 1 )fluoromethyl)(phenoxy)pho sphoryl ) -al aninate;propyl (((2-((9-(ethyl(3-fluorocyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-(ethyl(3-fluorocyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;isopropyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;ethyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(tetrahydrofuran-3-yl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5 -yl)methyl)(2,2,2 -trifluoroethoxy) phosphoryl) -alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl (((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl) (phenoxy)pho sphoryl) -alaninate;(3,3-difluorocyclobutyl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(3,3-difluorocyclobutyl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isopropyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isopropyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)atnino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3-(difluoromethyl)cyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 -y 1 )fluoromethyl)(phenoxy)pho sphoryl ) -al aninate;53MF-363534227Attorney Docket No.: 18395-20370.40propyl (((2-((9-((3-(difluoromethyl)cyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;3 -fluorocyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1.2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;3-fluorocyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;2 -ethylbutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;neopentyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;3-fluorocyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1.2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;3-fluorocyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isopropyl (ethoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;2-ethylbutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;neopentyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)aniino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)m ethyl) (phen oxy )pho sphoryl) -alaninate;isopropyl (ethoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (phenoxy )pho sphoryl) -alaninate;isopropyl (ethoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]lieptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(2,2,2- trifluoroethoxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(propoxy)phosphoryl)-alaninate;54MF-363534227Attorney Docket No.: 18395-20370.40cyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2, 2,2 -trifluoroethoxy )phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo| l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen-5- yl)fluoromethyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(2,2,2- trifluoroethoxy)phosphoryl)-alaninate;propyl (cyclopropoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;isopropyl (ethoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;isopropyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2, 2,2 -trifluoroethoxy )phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropy rrolo [ 1,2 -a] azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl (((2-((9-(ethyl((3-methyloxetan-3-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-(ethyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5 -yl)fluoromethyl)(phenoxy)pho sphoryl) -alaninate;propyl (((2-((9-(ethyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a |azocin-6-yl)carbamoyl)benzo[b |thiophen-5 - yl)fluoromethy 1) (phen ox y ) pho sphoryl) -alaninate;propyl (((2-((9-(ethyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro|2.4]heptane-4- carbonyl )decahydropyrrolo [ 1, 2 -a] azocin -6 -yl )carbam oyl)benzo [b]thi ophen-5 - yl)fluoromethyl) (phenoxy)pho sphoryl) -alaninate;cyclobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2, 2,2 -trifluoroethoxy )phosphoryl)-alaninate;isopropyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5 -yl)methyl)(2,2,2 -trifluoroethoxy) phosphoryl) -alaninate;isobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)aniino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4Jheptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[bJthiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;cyclobutyl (ethoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;55MF-363534227Attorney Docket No.: 18395-20370.40cyclobutyl (ethoxy(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;propyl (((2-((9-(ethyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y 1 )fluoromethyl)(phenoxy)pho sphoryl ) -al aninate;propyl (((2-((9-(ethyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)(2,2,2- trifluoroethoxy )phosphoryl)-alaninate;cyclobutyl (((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl) (phenoxy)pho sphoryl) -alaninate;cyclobutyl (((2-((9-((3-cyanocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo| l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (cyclopropoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;propyl (cyclopropoxy(fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl- 4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo [b]thiophen-5 -yl)methy l)phosphoryl)-alaninate;isopropyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-(ethyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo| l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen-5- yl)m ethyl) (ph enoxy)pho sphoryl ) -al aninate;isopropyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate 2,2,2-trifluoroacetate;isobutyl (cyclopropoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoy l)benzo [b]thiophen -5 -y l)methyl)phosphory 1 )-alaninate;cyclobutyl (ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl- 4-azaspiro[2,4]heptane-4-carbonyl)decaliydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;56MF-363534227Attorney Docket No.: 18395-20370.40cyclobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;propyl N-((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-O-methyl-serinate;propyl 2-(((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)amino)-2-methylpropanoate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryI)-phenylalaninate;isobutyl ((fluoro(2-((9-(methyl((3-(trifluoromethyl)cyclobutyl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;isobutyl (((2-((9-(((3-(difluoromethyl)cyclobutyl)methyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y 1 )fluoromethyl)(phenoxy)pho sphoryl ) -al aninate;isobutyl ((fluoro(2-((9-(methyl(2-(l-(trifluoromethyl)cyclopropyl)ethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)propyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluoro-3-methoxybutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-(((3-(difluoromethyl)cyclobutyl)methyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y 1 )fluoromethyl)(phenoxy)pho sphoryl ) -al aninate;propyl ((fluoro(2-((9-(methyl(2-(l-(trifluoromethyl)cyclopropyl)ethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)propyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]lieptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)propyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;57MF-363534227Attorney Docket No.: 18395-20370.40propyl (((2-((9-((3,3-difluorocyclopentyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5- yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane- 4-carbonyl)decahydropyrrolo| l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen-5- yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-morpholino-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)m ethyl) (phenoxy )pho sphoryl) -alaninate;propyl ((fluoro(2-((9-(methyl((3-methyloxetan-3-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(oxetan-3-yl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl N-(((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl) (phenoxy )pho sphoryl) -O-methy 1-serinate;propyl 2-((((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo[ 1,2-a ]azocin-6-yl)carbamoyl)benzo[b |thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)amino)-2-methylpropanoate;isopropyl 2-((((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)(phenoxy)phosphoryl)amino)butanoate;propyl ((difluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)prolinate;propyl l-(ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)phosphoryl)-3,3-difluoropyrrolidine-2 -carboxylate;propyl ((difluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;dipropyl 2,2'-(((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)bis(azanediyl))dipropionate;isobutyl (cyclopropoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methvl)phosphoryl)-alaninate;propyl l-(((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)amino)cyclopropane-l -carboxylate;isobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclopentyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclopentyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclopentyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;58MF-363534227Attorney Docket No.: 18395-20370.40(1-fluorocyclobutyl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(3,3,3-trifluoropropoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-(pyridin-3-yl)-4- azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-(pyridin-3-yl)-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((3-(7-methoxy-6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)-9-(methyl(3- (trifluoromethoxy)cyclobutyl)amino)-5-oxodecahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((3-(7-methoxy-6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)-9-(methyl(3- (trifluoromethoxy)cyclobutyl)amino)-5-oxodecahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3,3,3-trifluoro-2-methoxypropyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(2-(trifluoromethoxy)ethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(2-(trifluoromethoxy)ethyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2-oxopyrrolidin- 1 -yl)phosphoryl)-alaninate;cyclobutyl ((fluoro(2-((9-(methyl((3-methyloxetan-3-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbonyl)decahydropyrrolo [ 1,2-a] azocin-6-yl)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl((3-methyloxetan-3-yl)methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;(tetrahydrofuran-3-yl)methyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;isopropyl (ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;isopropyl (ethoxy(fluoro(2-((9-(methyl(4,4,4-trifluorobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-alaninate;propyl (ethoxy((2-((9-(ethyl(3-fluorocyclobutyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)phosphoryl)-alaninate;2-morpholinoethyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 -y 1 )fluoromethyl)(phenoxy)pho sphoryl ) -al aninate;59MF-363534227Attorney Docket No.: 18395-20370.40neopentyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)fluoromethyl)(phenoxy)phosphoryl)-alaninate;propyl (((2-((9-((3,3-difluoropropyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4- carbonyl)decahydropyrrolo| 1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5 - yl)fluoromethyl)(phenoxy)phosphoryl)-prolinate;2-methoxy-2-methylpropyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;6,6-difluorospiro[3.3]heptan-2-yl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro|2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(tetrahydrofuran-3-yl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(tetrahydrofuran-3-yl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl- 4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzofb]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(tetrahydro-2H-pyran-4-yl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;isobutyl 2-(((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[ l,2-a]azocin-6-yl)carbamoyl)benzo|b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)amino)butanoate;isopentyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl 2-(((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)amino)pentanoate;propyl ((cyclohexyloxy)(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;propyl ((cyclopentyloxy)(fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -yl)methyl)(i sopropoxy) phosphoryl) -alaninate;neopentyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(2-methoxyethoxy)phosphoryl)-alaninate;spiro[3.3]heptan-2-yl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-valinate;tetrahydrofuran-3-yl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;60MF-363534227Attorney Docket No.: 18395-20370.40tetrahydrofuran-3-yl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5 -y l)me thy 1)( phenoxy) phosphoryl) -alaninate;2 -fluoro-2 -methylpropyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1.2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(tetrahydrofuran-3-yl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl- 4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(tetrahydrofuran-3-yl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl- 4-azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;(tetrahydro-2H-pyran-4-yl)methyl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl 4,4-difluoro-1-((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)(phenoxy)phosphoryl)pyrrolidine-2-carboxylate; propyl N-((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbony l)decahydropyrrolo [ 1,2-a] azocin-6-y l)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(2,2,2-trifluoroethoxy)phosphoryl)-N-methyl-alaninate;2-ethylbutyl (ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6- phenyl-4-azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6- yl)carbamoyl)benzo[b]thiophen-5-yl)methyl)phosphoryl)-alaninate;propyl N-(ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-N-methyl-alaninate;propyl (ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)phosphoryl)-prolinate;spiro[3.4]octan-2-yl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro [2,4]heptan e-4-carbony l)decahydropyrrolo [ 1,2-a] azocin-6-y l)carbamoyl )benzo [b]thiophen - 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;spiro[2.3]hexan-5-yl ((fluoro(2-((9-((3-fluorocyclobutyl)(methyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate;propyl ((fluoro(2-((9-(methyl(3-(trifluoromethyl)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[l,2-a]azocin-6-yl)carbamoyl)benzo[b]thiophen- 5-yl)methyl)(phenoxy)phosphoryl)-alaninate,propyl 2-(((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(isobutoxy)phosphoryl)amino)-2-methylpropanoate; propyl 2-(((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-((S)-6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(isopropoxy)phosphoryl)amino)-2-methylpropanoate; propyl 2-((butoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)phosphoryl)amino)-2-methylpropanoate;propyl 2-(((fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2,4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)-2,3- dihydrobenzo[b]thiophen-5-yl)methyl)(propoxy)phosphoryl)amino)-2-methylpropanoate; and propyl 2-((ethoxy(fluoro(2-((9-(methyl(3-(trifluoromethoxy)cyclobutyl)amino)-5-oxo-3-(6-phenyl-4- azaspiro[2.4]heptane-4-carbonyl)decahydropyrrolo[1,2-a]azocin-6-yl)carbamoyl)-2,3-dihvdrobenzo [b]thiophen-5-yl)methyl)phosphoryl)amino)-2-methylpropanoate;61MF-363534227Attorney Docket No.: 18395-20370.40and pharmaceutically acceptable salts thereof.

[0114] In some embodiments, SBM is selected from the group consisting of parent drugs A3, A4, A5, A6, A7, A8, Al l, A13, A14, A18, A19, A20, A21, A22, A23, A25, A30, A32, A33, A35, A36, A37, A38, A40, A42, A43, A44, A47, A48, A49, A50, A52, A53, A55, A57, A58, A59, A60, A61, and A65, and pharmaceutically acceptable salts thereof. In some embodiments, SBM is selected from the group consisting of compounds A3, A4, A5, A6, A7, A8, Al l, A13, A14, A18, A19, A20, A21, A22, A23, A25, A30, A32, A33, A35, A36, A37, A38, A40, A42, A43, A44, A47, A48, A49, A50, A52, A53, A55, A57, A58, A59, A60, A61, and A65, prodrugs or intermediate metabolites thereof, and pharmaceutical ly acceptable salts of any of the foregoing.

[0115] In some embodiments, SBM is selected from the group consisting of prodrugs C4, C5, C6, C7. C8, CIO, C13, C17, C19, C23, C25, C53, C54, C61, C63, C64, C65, C66, C68, C70, C71, C73, C74, C75, C82, C83, C84, C89, C90, C91, C92, C93, C94, C96, C97, C96, C97, C102, C103, C015, C016, C017, C110, C111, C114, C116, Cl 18, C121, C122, CI23, C124, C125, C126, C127, C132, C133, C135, C136, C137, C140, C141, C143, C144, C148, C155, C156, C160, C162, C170, C173, C175, C176, C177, C180, C182, C185, C186, C188, Cl 89, Cl 94, Cl 95, Cl 97, Cl 98, C205, C208, and C209, and pharmaceutically acceptable salts thereof.

[0116] Any variation or embodiment of R10ia, R101b, R102, R103, R104, R104a, R104b, R105, Rp, Rpl, RP2, RPa, RPE, RPaal, RPaa2, RPaa3, RPaa4, Ring A, SBM, L, DIM, R10C, m, n, v, YDIM, DDIM, U, Rx, or any other variable provided herein can be combined with every' other variation or embodiment of R101a, R101b, R102, R103, R104, R104a, R104b, R105, Rp, RP1, RP2, RPa, RPE, RPaal, RPaa2, RPaa3, RPaa4, Ring A, SBM, L, DIM, R10C, m, n, v, YDIM, DDIM, U, Rx, or any other variable provided herein, the same as if each and every combination had been individually and specifically described.

[0117] As used herein, when any variable occurs more than one time m a chemical formula, its definition on each occurrence is independent of its definition at every other occurrence.Degradation Inducing Moiety (DIM)

[0118] In some embodiments, DIM is LBM. 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.62MF-363534227Attorney Docket No.: 18395-20370.40M. 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.

[0119] As defined herein and described below, wherein a formula is depicted usingsquare brackets, e g.,modifiable carbon, oxygen, or nitrogen atom within DIM or LBM including substitution or replacement of a defined group in DIM or LBM.

[0120] In certain embodiments, the present invention provides a compound of formula A, wherein LBM is a cereblon E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-aa:I-aaor a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described herein, and wherein: X1is a bivalent moiety selected from a covalent bond, CH2,CHCF3-, SO2 --S(O) P(O)R, P(O)R, P(O)NR2-C(O) - --C(S) -, or63MF-363534227Attorney Docket No.: 18395-20370.40X2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -CR2-, -NR-, -O-, -S-, or -Si(R2)-;R1is 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 R2is 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, -0C(0)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(0)(0R)2, -N(R)P(O)(OR)(NR2), -N(R)P(O)(NR2)2, or -N(R)S(O)2R;Ring A is a bi- or tn-cyclic ring selected from64MF-363534227Attorney Docket No.: 18395-20370.4065MF-363534227Attorney Docket No.: 18395-20370.40wherein 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 7-66MF-363534227Attorney Docket No.: 18395-20370.40membered 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; R3is selected from hydrogen, R6, halogen, -OR, -N(R)2, or -SR; each R4is independently hydrogen, -R°, 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, R5is hydrogen, Ci-4 aliphatic, or -CN; each R6is independently an optionally substituted group selected from Ci-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;L1is 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 or 4, each R is independently hydrogen, or an optionally substituted group selected from C1-6 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, ortwo 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.

[0121] Where a point of attachment of-(R2)mis depicted on Ring B, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of -(R2)mmay 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 - R2is attached to a nitrogen atom bound to R4or R5, R4or R5is absent and -R2takes the place of the R4or R5group. Where -R2is attached to a carbon atom bound to R3, RJis absent and -R2takes the place of the RJgroup.67MF-363534227Attorney Docket No.: 18395-20370.40

[0122] In some embodiments, a compound of formula I-aa above is provided as a compound of formula I-aa' or formula I-aa":i-aa"or a pharmaceutically acceptable salt thereof, wherein:each of SBM, Ring A, L, L1, R1, R2, X1, X2, X3, and m is as defined above.

[0123] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-bb:or a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring A, L, R1, R2, X1, and m is as defined above.

[0124] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-cc:68MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein:X1is a bivalent moiety selected from a covalent bond, —CH2—, -CHCF3-, -SO2-, -S(O)-, -P(O)R- -P(O)R- -P(O)NR.2- -C(O) - -C(S) or; X2is a carbon atom or silicon atom; X3is a bivalent moiety selected from -CR2-, -NR-, -O-, -S-, or -Si(R2)-;R1is 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,69MF-363534227Attorney Docket No.: 18395-20370.40each of R2and R3ais 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 partially70MF-363534227Attorney Docket No.: 18395-20370.40unsaturated 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;each R4is 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, R5is hydrogen, C1-4 aliphatic, or -CN; each R6is independently an optionally substituted group selected from C1-6 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;L1is 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 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; and p is 0 or 1, wherein when p is 0, the bondf S8M j - 1- — Iconnecting Ring C and Ring D is connected to5; and each R is independently hydrogen, or an optionally substituted group selected from C1-6 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, ortwo 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, m addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.

[0125] In some embodiments, a compound of formula I-cc above is provided as a compound of formula I-cc' or formula I-cc":71MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring C, Ring D, L, L1, R1, R2, R3a, X1, X2, X3, n, m, and p is as defined above.

[0126] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-dd:- pI-ddor a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring C, Ring D, L, R1, R2, R3a, X1, n, m, and p is as defined above.

[0127] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-ee:72MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: X1is a bivalent moiety selected from a covalent bond, CH2-, -CHCF3 -, -SO2 --S(O)--, P(O)R -, P(O)R, P(O)NR2, -C(O) -,A xz\'’z-C(S) or *; X2is a carbon atom or silicon atom, X3is a bivalent moiety selected from -CR2-, -NR-, -O-, -S-, or -Si(R2)~; R1is hydrogen, deuterium, halogen, -CN, -OR, - SR, -S(O)R, -S(O)2R; -NR2, -P(O)(OR)2, -P(O)(NR2)2, -SI(OH)2R, -SI(OH)(R)2, -SiR3, or an optionally substituted C 1-4 aliphatic;Ring C is a mono- or bicyclic ring selected from73MF-363534227Attorney Docket No.: 18395-20370.4074MF-363534227Attorney Docket No.: 18395-20370.4075MF-363534227Attorney Docket No.: 18395-20370.40each of R2andR3ais independently hydrogen, deuterium, -R6, halogen, -CM, -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 -membered76MF-363534227Attorney Docket No.: 18395-20370.40saturated 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;each R4is 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(0)NR2, or -N(R)S(0)2R, R5is hydrogen, C1-4 aliphatic, or -CN; each R6is independently an optionally substituted group selected from C1-6 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;L1is 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 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 C1-6 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, ortwo 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.

[0128] In some embodiments, a compound of formula I-ee above is provided as a compound of formula I-ee' or formula I-ee":77MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring C, Ring D, L, L1, R1, R2, R3a, X1, X2, X3, m, n, and p is as defined above.

[0129] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an F23 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-ff:or a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring C, Ring D, L, LR1, R2, R3a, X1, m, n, and p is as defined above.78MF-363534227Attorney Docket No.: 18395-20370.40

[0130] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-gg:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: X1is a bivalent moiety selected from a covalent bond, CH2-, -CHCF3 SO2-S(O) -, -P(O)R -, -P(O)R -, P(O)NR2, C(O) -,-C(S) or *; X2is a carbon atom, nitrogen atom, or silicon atom, X3is a bivalent moiety selected from a covalent bond, -CR2~, -NR-, -O-, -S-, or -SiR2~;R1is absent, 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)R2, -SiR3, or an optionally substituted CM aliphatic; each R is independently hydrogen, or an optionally substituted group selected from Ci-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, ortwo 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 R2is independently hydrogen, deuterium, -R6, halogen, -CN, -NO2, -OR, -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)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;79MF-363534227Attorney Docket No.: 18395-20370.40each R6is independently an optionally substituted group selected from Ci-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 Ring E, Ring F, and Ring G is independently and optionally substituted with 1-2 oxo groups;L1is 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-; and m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16.fsBMj - L — |

[0131] Where a point of attachment ofx''— * 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 pointf sBIVH - 1- — |of attachment of5may be on any avai lable carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the ring to which Ring E or Ring G is fused to Ring F.

[0132] Where a point of attachment of-(R2)mis 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)mmay 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 is fused to Ring F.80MF-363534227Attorney Docket No.: 18395-20370.40R1 / ---X3<- \ ( \| 2^0

[0133] Where a point of attachment of X1— NH is depicted on Ring E, Ring F, or Ring G, it is intended, and one of ordinary skill would appreciate, that the point of attachment of1— Lmay 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 is fused to Ring F.

[0134] In some embodiments, a compound of formula I-gg above is provided as a compound of formula I-gg' or formula I-gg":I-gg”or a pharmaceutically acceptable salt thereof, wherein: each of SBM, Ring E, Ring F, Ring G, L, L1, R1, R2, X1, X2, X3, and m is as defined above.

[0135] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-gg-1 or I-gg-2:81MF-363534227Attorney Docket No.: 18395-20370.40&-gg-1I-gg-2or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein each R2is independently hydrogen, deuterium, -R6, halogen, ( \. -NO2, -OR, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2;-S(O)R, -C(O)R, -C(O)OR, -C(C))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 R6is independently an optionally substituted group selected from C1-6 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 Ring E, Ring F, and Ring G is independently and optionally substituted with 1-2 oxo groups;82MF-363534227Attorney Docket No.: 18395-20370.40each R is independently hydrogen, or an optionally substituted group selected from Ci- 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, ortwo 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;E1is 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.( SBM J L

[0136] 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 Ring E or Ring G is fused to Ring F.

[0137] 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 is fused to Ring F.

[0138] Where a point of attachment of / P oll / ™7\ R10x — rK| -Li- v / . -Li—oris depicted on Ring E, Ring F, or 83MF-363534227Attorney Docket No.: 18395-20370.40Ring G, it is intended, and one of ordinary skill in the art would appreciate, that the point ofRu> * •> < attachment o or W --NHmay |^e on anyf available carbon or nitrogen atom on Ring E, Ring F, or Ring G, including the carbon atom to which Ring E or Ring G is fused to Ring F.

[0139] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-hh:I-hhor a pharmaceutically acceptable salt thereof, wherein: each of SBM, Ring E, Ring F, Ring G, L, R1, R2, X1, and m is as defined above.

[0140] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-ii:1 -iior a pharmaceutically acceptable salt thereof, wherein L and SMB are as defined above and described in embodiments herein, and wherein: X1is a bivalent moiety selected from a covalent bond, -CH2-, -CHCF3-, -SO2-, -S(O)-, -P(O)R-, -P(O)R-, -P(O)NR2~, -C(O) -,—C(S) -, or84MF-363534227Attorney Docket No.: 18395-20370.40X2is a carbon atom, nitrogen atom, or silicon atom;X3is a bivalent moiety selected from a covalent bond, --CR2-, -NR-, -O-, -S-, or -S1R2-;R1is absent, 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)R2, -SiR3, or an optionally substituted C1-4 aliphatic;each R is independently hydrogen, or an optionally substituted group selected from C1-6 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, ortwo 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 R2is independently hydrogen, deuterium, -R6, halogen, --CN, --NO2, OR, -SR, -N(R)2, - S1(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( )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 R6is independently an optionally substituted group selected from C1-6 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 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,85MF-363534227Attorney Docket No.: 18395-20370.40Ring 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;L1is 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 -0-, -C(0)-, -C(S)-, -C(R)2-, -CH(R)-, -C(F)2-, -N(R)-, -S-, -S(0)2- or - (C)=CH-; m is 0, 1, 2, 3, or 4.

[0141] Where a point of attachment ofis depicted on Ring E or Ring H, it is intended, and one of ordinary skill in the art would appreciate, that the point ofattachment of or Ring H including the carbon atom to which Ring E and Ring H are fused.

[0142] Where a point of attachment of-(R2)mis depicted on Ring E and Ring H, it is intended, and one of ordinary' skill m 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.R1X3, \ / \L1— x2 / >=O

[0143] Where a point of attachmentof 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 R1-X3| - * 1attachment of X —N?H may be on anyavailable carbon or nitrogen atom on Ring E or Ring H including the carbon atom to which Ring E and Ring H are fused.

[0144] In some embodiments, a compound of formula I-ii above is provided as a compound of formula I-ii or formula I-ii”:86MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring E, Ring H, L, L1, R1, R2, X1, X2, X3, and m is as defined above.

[0145] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-kk:1-kkor a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring E, Ring H, L, R1, R2, X1, and m is as defined above.

[0146] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula 1-11:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein:1is a bivalent moiety selected from a87MF-363534227Attorney Docket No.: 18395-20370.40covalent bond, -CH2-, -CHCF3-, -SO?-, -S(O)-, -P(O)R- -P(O)R- -P(O)NR2-, -C(O) -,"ft.-C(S) - or, X2is a carbon atom, nitrogen atom, or silicon atom; X3is a bivalent moiety selected from a covalent bond, CR?, -NR--, - 0 -S or - SiR2R1is absent, hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)? R, -NR2, -P(O)(OR)2, - P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -SI(OH)R2, -SiR3, or an optionally substituted C1-4 aliphatic,each R is independently hydrogen, or an optionally substituted group selected from Ci- 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 R2is independently hydrogen, deuterium, -R6, halogen, -CN, -NO2, -OR, -SR, -N(R)2, - Si(R)3, -S(O)2R, -S(O)? N(R)?, -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 R6is independently an optionally substituted group selected from C1-6aliphatic, 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 with 1-3 heteroatoms independently88MF-363534227Attorney Docket No.: 18395-20370.40selected 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 5-12 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;L1is a covalent bond or a Ci-3 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein 1-2 methylene units of the chain are independently and optionally replaced with -0-, -C(0)-, -C(S)-, -C(R)2-, -CH(R )-, -C(F)2-, -N(R)-, -S-, -S(0)2- or - (C)=CH-; and m is 0, 1, 2, 3, or 4.( SBM ) - L. — I

[0147] Where a point of attachment ofW— ' * 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 pointfsBMj - L — |of attachment ofx'"-—5may 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.

[0148] 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)™ 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.R1y — X3£ —X2

[0149] Where a point of attachment of X1—NH is depicted on Ring I, Ring J, and Ring K, it is intended, and one of ordinary skill in the art would appreciate, thatR1 —X3£;__.L1 ___X4 \ — ithe point of attachment of ~~NH may be on any available carbon or nitrogen atom on Ring I, Ring J, or Ring K, including the atom to which Ring 1, Ring J, and Ring K are fused.89MF-363534227Attorney Docket No.: 18395-20370.40

[0150] In some embodiments, a compound of formula 1-11 above is provided as a compound of formula 1-11' or formula I-ll":or a pharmaceutically acceptable salt thereof, wherein each of SBM, Ring I, Ring J, Ring K, L, L1, R1, R2, X1, X2, X3, and m is as defined above.

[0151] In certain embodiments, the present invention provides a compound of formula I-mm:or a pharmaceutically acceptable salt thereof, wherein: each of SBM, Ring I, Ring J, Ring K, L, R1, R2, X1, and m is as defined above.

[0152] As described above, in another aspect, the present invention provides a compound of Formula I-nn:or a pharmaceutically acceptable salt thereof, wherein90MF-363534227Attorney Docket No.: 18395-20370.40Ring M is selected fromeach of X1, X6, and X7is independently a bivalent moiety selected from a covalent bond, - CH2-, -CHCF3-, -SO2-, -S(O)~, -P(O)R~, -P(O)R~, -P(O)NR2-, -CO -C(S) oreach of X3and X5is independently a bivalent moiety selected from a covalent bond, -CR2--, - NR-, O -, - S-, or Si R2X4is a trivalent moiety selected fromeach R is independently hydrogen, or an optionally substituted group selected from C1-6aliphatic, 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;91MF-363534227Attorney Docket No.: 18395-20370.40each R3ais independently hydrogen, deuterium, -R6, halogen, -CN, -NO2, -OR, -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)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° is independently an optionally substituted group selected from C1-6 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' is independently hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2-NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)R2, -Si(OH)2R, -SiR3, or an optionally substituted CM aliphatic;or R7and X1or X3are 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' 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' 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 D 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,92MF-363534227Attorney Docket No.: 18395-20370.40silicon, or sulfur, or 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;L1is 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-; n is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0153] As defined above and described herein, each of X1, X6, and X7is independently a bivalent moiety selected from a covalent bond, -CH2--, --CIICF3--, --SO2-, -S(O)--, -P(O)R-,OO-P(O)R- -P(O)NR2- -C(O) -C(S) or.

[0154] In some embodiments, each of X1, X6, and X7is independently a covalent bond. In some embodiments, each of X1, X6, and X7is independently -CH2-. In some embodiments, each of X1, X6, and X7is independently -CR2 In some embodiments, each of X1, X6, and X7is independently --C(O) In some embodiments, each of X1, X°, and X7is independently ~C(S)“ In some embodiments, each of X1, X6, and X ' is independently ~CH(R)~ In some embodiments, each of X1, X6, and X7is independently - CHfCFs)-. In some embodiments, each of X1, X6, and X7is independently -P(O)(OR)-. In some embodiments, each of X1, X6, and X7is independently ~P(O)(R)-. In some embodiments, each of X1, X6, and X7is independently P(O)N 2. In some embodiments, each of X1, X6, and X' is independently - S(O)~. In some embodiments, each of X1, X6, and X7is independently -S(O)2~. In some Oembodiments, each of X1, X6, and X7is independently,

[0155] In some embodiments each of X1, X6, and X7is independently selected from the compounds described herein.

[0156] As defined above and described herein, X2is a carbon atom, nitrogen atom, or silicon atom.

[0157] In some embodiments, X2is a carbon atom. In some embodiments, X2is a nitrogen atom. In some embodiments, X2is a silicon atom.93MF-363534227Attorney Docket No.: 18395-20370.40

[0158] In some embodiments, X2is selected from the compounds described herein.

[0159] As defined above and described herein, X3is a bivalent moiety selected from - CH2-, -CR2-, -NR-, -CF2-, -CHF- -S-, -CH(R)-, -SIR2-, or -O-.

[0160] In some embodiments, each of X3and X3is independently CH2In some embodiments, each of X3and X3is independently -CR2In some embodiments, each of X3and X5is independently -NR- In some embodiments, each of X3and X3is independently — CF2—. In some embodiments, each of X3and X5is independently -CHF- In some embodiments, each of X and X5is independently -S-, In some embodiments, each of X3and X5is independently -CH(R)-. In some embodiments, each of X3and X5is independently -SIR2-. In some embodiments, each of X3and X5is independently -O

[0161] In some embodiments, each of X3and X5is independently selected from the compounds described herein.

[0162] As defined above and described herein, X4is a tri valent moiety selected from

[0163] In some embodiments, X4isIn some embodiments, X4isIn some embodiments, X4isIn some embodiments, X4is. In someembodiments, X4is ■

[0164] In some embodiments, X4is selected from the compounds described herein.

[0165] As defined above and described herein, R1is 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)R2, -SiR3, an optionally substituted Ci-4 aliphatic, or R1and X1or X4are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated,94MF-363534227Attorney Docket No.: 18395-20370.40carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from nitrogen, oxygen, or sulfur.

[0166] In some embodiments, Rlis hydrogen. In some embodiments, R1is deuterium. In some embodiments, R1is halogen. In some embodiments, R1is -CN. In some embodiments, R1is -OR In some embodiments, R1is -SR. In some embodiments, R1is -S(O)R. In some embodiments, R1is -S(O)2R. In some embodiments, Rlis -NR2. In some embodiments, R1is P(O)(OR)2. In some embodiments, R1is P(O)(NR2)OR. In some embodiments, Rlis - P(O)(NR2)2. In some embodiments, R1is -SifOHhR. In some embodiments, R1is -Si(OH)R2. In some embodiments, R1is -SiR?. In some embodiments, R1is an optionally substituted Ci-4 aliphatic. In some embodiments, R1and X1or X4are 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.

[0167] In some embodiments, Rlis selected from the compounds described herein.

[0168] As defined above and described herein, each R is independently hydrogen, deuterium, or an optionally substituted group selected from Ci-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.

[0169] In some embodiments, R is hydrogen. In some embodiments, R is deuterium. In some embodiments, R is optionally substituted Ci-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 their95MF-363534227Attorney Docket No.: 18395-20370.40intervening 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.

[0170] In some embodiments, R is selected from the compounds described herein.

[0171] As defined above and described herein, each of R2and R3ais independently hydrogen, deuterium, -R6, 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.

[0172] In some embodiments, R2and / or R3ais hydrogen. In some embodiments, R2and / or R3ais deuterium. In some embodiments, R2and / or R3ais R6. In some embodiments, R2and / or R3ais halogen. In some embodiments, R2and / or R3ais -CN. In some embodiments, R2and / or R3ais -NO2. In some embodiments, R2and / or R3ais -OR. In some embodiments, R2and / or R3ais -Si(OH)2R. In some embodiments, R2and / or R3ais -Si(OH)R2. In some embodiments, R2and / or R3ais -SR. In some embodiments, R2and / or R3ais -NR2. In some embodiments, R2and / or R3ais -SiR3. In some embodiments, R2and / or R3ais -S(O)2R. In some embodiments, R2and / or R3ais -S(O)2NR2. In some embodiments, R2and / or R3ais -S(O)R. In some embodiments, R2and / or R3ais -C(O)R In some embodiments, R2and / or R3ais -C(O)OR. In some embodiments, R2and / or R3ais -C(O)NR2. In some embodiments, R2and / or R3ais C(O)N(R)OR. In some embodiments, R2and / or R3ais -C(R)2N(R)C(O)R In some embodiments, R2and / or R3ais -C(R)2N(R)C(O)NR2In some embodiments, R2and / or R3ais - OC(O)R. In some embodiments, R2and / or R3ais -OC(O)NR2. In some embodiments, R2and / or R3ais -OP(O)R2. In some embodiments, R2and / or R3ais -OP(O)(OR)2In some embodiments, R2and / or R3ais - OP(O)(OR)NR2In some embodiments, R2and / or R3ais -OP(O)(NR2)2-. In some embodiments, R2and / or R3ais -N(R)C(O)OR. In some embodiments, R2and / or R3ais -N(R)C(O)R. In some embodiments, R2and / or R3ais -N(R)C(O)NR2. In some embodiments, R2and / or R3ais -NP(O)R2. In some embodiments, R2and / or R3ais -N(R)P(O)(OR)2. In some embodiments, R2and / or R3ais -N(R)P(O)(OR)NR2. In some embodiments, R2and R3ais independently -N(R)P(O)(NR2)2. In some embodiments, R2and / or R3ais - N(R)S(O)2R.96MF-363534227Attorney Docket No.: 18395-20370.40

[0173] In some embodiments, R2and R3ais independently -OH. In some embodiments, R2and / or R3ais -Nth In some embodiments, R2and / or R3ais -CEI2NH2. In some embodiments, R2and / or R3ais - CH2NHCOMe. In some embodiments, R2and / or R3ais -CH2NHCONHMe. In some embodiments, R2and / or R3ais -NHCOMe. In some embodiments, R2and / or R3ais -NHCONHEt. In some embodiments, R2and / or R3ais -SiMe3. In some embodiments, R2and / or R3ais -SiMe2OH. In some embodiments, R2and / or R3ais -SiMe(OH)2. In some embodiments R2and / or R3aislIn some embodiments.R2and / or R3ais Br. In some embodiments, R2and / or R3ais Cl. In some emodiments, R2and / or R3ais F. In some embodiments, R2and / or R3ais Me. In some embodiments, R2and / or R3ais -NHMe. In some embodiments, R2and / or R3ais -NMe2. In some embodiments, R2and / or R3ais -NHCC Et In some embodiments, R2and / or R3ais -CN. In some embodiments, R2and / or R3ais -CI Ph. In some embodiments, R2and / or R3ais -NHCChtBu. In some embodiments, R2and / or R3ais -CChtBu. In some embodiments, R2and / or R3ais - OMe. In some embodiments, R2and / or R3ais -CF3.

[0174] In some embodiments, R2or R3ais selected from the compounds described herein.

[0175] As defined above and described herein, R3is hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -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.

[0176] In some embodiments, R3is hydrogen. In some embodiments, R3is deuterium. In some embodiments, R3is halogen. In some embodiments, R3is -CN. In some embodiments, R3is “ O2. In some embodiments, R3is -OR. In some embodiments, R3is -NR2. In some embodiments, R3is -SR. In some embodiments, R3is -S(O)2R. In some embodiments, R3is -S(O)2NR2 In some embodiments, R3is - S(O)R. In some embodiments, R3is -C(O)R In some embodiments, R3is -C(O)OR. In some embodiments, R3is C(O)NR2. In some embodiments, RJis -C(O)NR(OR). In some embodiments, R3is -OC(O)R. In some embodiments, RJis -OC(O)NR2. In some embodiments, R3is -OP(O)(OR)2. In some embodiments, RJis -OP(O)(NR2) In some embodiments, RJis -OP(O)(OR)NR2. In some embodiments, R3is - N(R)C(O)R. In some embodiments, R3is -N(R)C(O)OR. In some 97MF-363534227Attorney Docket No.: 18395-20370.40embodiments, R3is -N(R)C(O)NR2. In some embodiments, R3is -N(R)S(O)2R. In some embodiments, R3is -N(R)S(O)2NR2. In some embodiments, R3is -N(R)P(O)(OR)2. In some embodiments, RJis N(R)P(O)(OR)NR2. In some embodiments, R3is -P(O)(OR)2. In some embodiments, RJis “P(O)(NR2)OR. In some embodiments, R3is “P(O)(NR2)2. In some embodiments, RJis -Si(OH)2R. In some embodiments, R3is -Si(OH)(R)2. In some embodiments, R3is -Si(R)3.

[0177] In some embodiments, R3is methyl. In some embodiments, R3is -OCH3. In some embodiments, RJis chloro.

[0178] In some embodiments, R3is selected from the compounds described herein.

[0179] As defined above and described herein, each R4is 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.

[0180] In some embodiments, R4is hydrogen. In some embodiments, R4is -R°. In some embodiments, R4is halogen. In some embodiments, R4is -CN. In some embodiments, R4is -NO2. In some embodiments, R4is OR. In some embodiments, R4is SR. In some embodiments, R4is -NR2. In some embodiments, R4is -S(O)2R. In some embodiments, R4is -S(O)2NR2. In some embodiments, R4is - S(O)R. In some embodiments, R4is -C(O)R. In some embodiments, R4is -C(O)OR. In some embodiments, R4is -C(O)NR2. In some embodiments, R4is -C(O)N(R)OR. In some embodiments, R4is -OC(O)R. In some embodiments, R4is -OC(O)NR2. In some embodiments, R4is -N(R)C(O)OR. In some embodiments, R4is -N(R)C(O)R. In some embodiments, R4is -N(R)C(O)NR2. In some embodiments, R4is -N(R)S(O)2R. In some embodiments, R4is -P(O)(OR)2. In some embodiments, R4is -P(O)(NR2)OR. In some embodiments, R4is -P(O)(NR2)2.

[0181] In some embodiments, R4is methyl. In some embodiments, R4is ethyl. In some embodiments, R4is cyclopropyl.

[0182] In some embodiments, R4is selected from the compounds described herein.

[0183] As defined above and described herein, R5is hydrogen, deuterium, an optionally substitute Ci - 4 aliphatic, or -CN.98MF-363534227Attorney Docket No.: 18395-20370.40

[0184] In some embodiments, R5is hydrogen. In some embodiments, R5is deuterium. In some embodiments, R;is an optionally substituted C1-4 aliphatic. In some embodiments, R5is --CN.

[0185] In some embodiments, R5is selected from the compounds described herein.

[0186] As defined above and described herein, each R6is independently an optionally substituted group selected from Ci-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.

[0187] In some embodiments, R6is an optionally substituted Ci-6 aliphatic. In some embodiments, R6is an optionally substituted phenyl. In some embodiments, R6is 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, R6is an optionally substituted 5-6 membered heteroaryl ring having 1 -4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0188] In some embodiments, R6is selected from the compounds described herein.

[0189] As defined generally above, each R' 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 CM aliphatic, or R1and X1or X3are 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 R7groups 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 R7groups 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, bridged99MF-363534227Attorney Docket No.: 18395-20370.40heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.

[0190] In some embodiments, R7is hydrogen. In some embodiments, R7is deuterium. In some embodiments, R7is halogen. In some embodiments, R7is -CN. In some embodiments, R' is -OR. In some embodiments, R7is -SR. In some embodiments, R7is -S(O)R In some embodiments, R7is S(O)2R. In some embodiments, R7is -NR2. In some embodiments, R7is -Si(R)3. In some embodiments, R' is - P(O)(R)2. In some embodiments, R7is -P(O)(OR)2. In some embodiments, R' is -P(O)(NR2)OR. In some embodiments, R7is -P(O)(NR2)2 In some embodiments, R7is -Si(OH)R2. In some embodiments, R' is - Si(OH)2R. In some embodiments, R7is an optionally substituted C1-4 aliphatic. In some embodiments, R7and X1or X3are 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 R7groups 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 R7groups 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 R7groups 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.

[0191] In some embodiments, R7is selected from hydrogen, halogen, -CN, -OR, -NR2, or Ci-4 alkyl. In some embodiments, R7is selected from hydrogen, halogen, -CN, or CM alkyl. In some embodiments, R7is fluoro. In some embodiments, two R7groups on the same carbon are optional ly taken together with their intervening atoms to form a 3- or 4- membered spiro fused ring.

[0192] In some embodiments, R7is selected from the compounds described herein.100MF-363534227Attorney Docket No.: 18395-20370.40

[0193] As defined above and described herein. Ring A is a bi- or tricyclic ring selected from101MF-363534227Attorney Docket No.: 18395-20370.40

[0194] In some embodiments. RingA is °. In some embodiments, Ring Ais. In some embodiments, Ring A is. In some102M -363534227Attorney Docket No.: 18395-20370.40embodiments, RingA is In some embodiments. RingA isIn some embodiments, RingA is In some embodiments, Ring A isIn some embodiments, Ring A is. In some embodiments,Ring Ais In some embodiments, RingA is. In someembodiments, RingA is. In some embodiments, RingA isIn some embodiments, RingA is In some embodiments, Ring A isIn some embodiments, Ring A is. In some embodiments,In some embodiments. Ring A isembodiments, Ring A isIn some embodiments, Ring A is103MF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, Ring A is. In some V-jembodiments, Ring A is'. In some embodiments, Ring A isIn some embodiments. Ring A is In some embodiments,Ring Ais In some embodiments, RingA is. In someembodiments, Ring AisIn some embodiments. Ring Ais In some embodiments, Ring A isIn some embodiments, Ring A is In some embodiments,Ring Ais In some embodiments. RingA isembodiments, RingA is In some embodiments, RingA isIn some embodiments, RingA is In some embodiments, Ring A is104MF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, Ring A is. In some embodiments,Ring Ais In some embodiments. RingA is. In some embodiments, RingA is In some embodiments. RingA is In some embodiments, RingA is In some embodiments, Ring A isIn some embodiments. Ring A iss. In some embodiments.In some embodiments, Ring A isembodiments. RingA is In some embodiments, RingA isIn some embodiments, RingA is In some embodiments, Ring A is105MF-363534227Attorney Docket No.: 18395-20370.40s. In some embodiments, Ring A is?. In some embodiments.Ring Ais. In some embodiments, RingA is. Insome embodiments, RingA is. In some embodiments, Ring A is'c im.. In some embodiments, Ring A is. In someP2)., Nembodiments, RingA is. In some embodiments, Ring A is£. In some embodiments, Ring A is. In some (R%“f 8embodiments, RingA is. In some embodiments, RingA is * R®RIn some embodiments. RingA is In some embodiments. Ring A isB'}■m1. In some embodiments, Ring A is106MF-363534227Attorney Docket No.: 18395-20370.40

[0195] In some embodiments, Ring A is selected from the compounds described herein.

[0196] 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 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;

[0197] 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 I -4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur.

[0198] In some embodiments. RingB is In some embodiments. Ring BIn some embodiments. Ring B is

[0199] In some embodiments, Ring B is selected from the compounds described herein.107MF-363534227Attorney Docket No.: 18395-20370.40

[0200] In some embodiments. Ring A and RingB is. In someembodiments. Ring A and RingB is °. In some embodiments, Ring A andRing Bis In some embodiments. Ring A and Ring Bis

[0201] As defined above and described herein. Ring C is a mono- or bicyclic ring selected from108MF-363534227Attorney Docket No.: 18395-20370.40

[0202] In some embodiments. RingC is O In some embodiments, Ring Cis 47 O. In some embodiments, Ring C is 1 O. In some embodiments.Ring Cis In some embodiments, RingC is ®. In someembodiments, RingC is. In some embodiments, RingC isIn some embodiments. RingC is In some embodiments, Ring C is(RA®. In some embodiments. Ring C isG. In some embodiments,Ring Cis. In some embodiments, RingC is. In some(b' 'Irrrembodiments. RingC is. In some embodiments, RingC is NR5. Insome embodiments, RingC is. In some embodiments, Ring C is109MF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, Ring C is In some embodiments.In some embodiments. Ring C is In some embodiments, Ring Cis some embodiments, RingC is

[0203] In some embodiments, RingC is In some embodiments, Ring Cis In some embodiments, Ring C is. In some embodiments, Ring Cis In some embodiments. RingC is In someembodiments. RingC is In some embodiments, Ring C issome embodiments, RingC is In some embodiments, Ring C is110MF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, Ring C is In some embodiments. Ring C isIn some embodiments, RingC is. In some embodiments. RingC is In some embodiments, RingC is In some embodiments, RingC is In some embodiments, Ring C isIn some embodiments. Ring C is

[0204] In some embodiments, Ring C is a mono- or bicyclic ring selected from111MF-363534227Attorney Docket No.: 18395-20370.40112MF-363534227Attorney Docket No.: 18395-20370.40113MF-363534227Attorney Docket No.: 18395-20370.40

[0205] In some embodiments. Ring C is selected from the compounds described herein.

[0206] As defined above and described herein, Ring D 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;

[0207] In some embodiments. Ring D is a 6 to 10-membered aryl. In some embodiments. Ring D is a 6 to 10-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 I) 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.

[0208] In some embodiments, Ring D phenyl. In some embodiments, Ring D pyridyl. In some embodiments. Ring D is indazole. In some embodiments. Ring D is isoquinoline. In some embodiments. Ring D is imidazo[l,2-a]pyndine.

[0209] In some embodiments, Ring D is selected from the compounds described herein.

[0210] 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 with 1-3 heteroatoms independently selected from boron.114MF-363534227Attorney Docket No.: 18395-20370.40nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1- 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, wherein Ring E, Ring F, and Ring G is independently and optionally substituted with 1-2 oxo groups.

[0211] In some embodiments, each of Ring E, Ring F, and Ring G is independently a fused ring selected from 6-membered aryl. In some embodiments, each of Ring E, Ring F, and Ring G is independently a fused ring selected from 6-membered heteroaryl containing 1 - 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, each of Ring E, Ring F, and Ring G is independently a fused ring selected from a 5 to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, each of Ring E, Ring F, and Ring G is independently a fused ring selected from 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 of Ring E, Ring F, and Ring G is independently a fused ring selected from a 5-membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. In some embodiments, Ring E, Ring F, and Ring G is independently and optionally substituted with 1 - 2 oxo groups.

[0212] In some embodiments. RingF is

[0213] In some embodiments, each of Ring E and Ring G is independentlyR2k. In some embodiments, each of Ring E and Ring G is independentlyIn some embodiments, each of Ring E and Ring G is independentlyIn some embodiments, each of Ring E and Ring G is independently115MF-363534227Attorney Docket No.: 18395-20370.40-. In some embodiments, each of Ring E and Ring G is independentlyN'A

[0214] In some embodiments. Ring E, Ring F, and RingG issome embodiments. Ring E, Ring F, and RingG isembodiments, Ring E, Ring F, and RingG is

[0215] In some embodiments, Ring E, Ring F, and Ring G is selected from the compounds described herein.

[0216] 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.

[0217] 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.116MF-363534227Attorney Docket No.: 18395-20370.40

[0218] 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 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

[0219] 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 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.

[0220] In some embodiments, Ring I and Ring J is selected from the compounds described herein.

[0221] As defined above and described herein. Ring K is a fused ring selected from a 5- 12 membered saturated or partially unsaturated carbocyclyl or heterocyclyl 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.

[0222] In some embodiments, Ring K is a fused ring selected from a 5-12 membered saturated or partially unsaturated carbocyclyl. In some embodiments, Ring K is a 5-12 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 a fused 5-6 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.117MF-363534227Attorney Docket No.: 18395-20370.40

[0223] In some embodiments, Ring I, Ring J, and Ring Kis

[0224] In some embodiments. Ring K is selected from the compounds described herein.

[0225] As defined above and described herein, Ring M is selected from

[0226] In some embodiments, Ring M is. In some embodiments, RingM is O. In some embodiments, Ring M is ®. In some embodiments,RingM is, In some embodiments. Ring Mis ®. In some118MF-363534227Attorney Docket No.: 18395-20370.40embodiments, RingM is. In some embodiments. RingM is 0. Insome embodiments, Ring Mis O In some embodiments. RingM isIn some embodiments. Ring M is

[0227] In some embodiments. Ring M is selected from the compounds described herein.

[0228] As defined above and described here, L1is 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-;

[0229] In some embodiments, L1is a covalent bond. In some embodiments, L1is a C1-3 aliphatic. In some embodiments, L1is CH2 In some embodiments, L1is C(D)(H)-. In some embodiments, L1is - C(D)2~. In some embodiments, L1is -CH2CH2-. In some embodiments, L1is -NR-. In some embodiments, L1is -NH-. In some embodiments, L1is -NMe-. In some embodiments, L1is -NEt-~. In some embodiments, L1is --CH2NR--. In some embodiments, L1is or -O-. In some embodiments, L1is - CI I2O-. In some embodiments, L1is — S—. In some embodiments, L1is -OC(O)-. In some embodiments, L1is -C(O)O-. In some embodiments, L1is -C(O)-. In some embodiments, L1is -S(O)-. In some embodiments, L1is -S(O)2-,. In some embodiments, L1is -NRS(O)2-. In some embodiments, L1is -S(O)2NR-. In some embodiments, L1is -NRC(O)-. In some embodiments, L1is -C(O)NR-.

[0230] In some embodiments. L1is selected from the compounds described herein.119MF-363534227Attorney Docket No.: 18395-20370.40

[0231] As defined above and described herein, ™ is a single or double bond.

[0232] In some embodiments, ™ is a single bond. In some embodiments, ™ is a double bond.

[0233] In some embodiments, ™ is selected from the compounds described herein.

[0234] 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.

[0235] 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.

[0236] In some embodiments, m is selected from the compounds described herein.

[0237] As defined above and described herein, n is 0, 1, 2, 3 or 4.

[0238] 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.

[0239] In some embodiments, n is selected from the compounds described herein.

[0240] As defined above and described herein, p is 0 or 1.

[0241] In some embodiments, p is 0. In some embodiments, p is 1.

[0242] In some embodiments, p is selected from the compounds described herein.

[0243] As defined above and described herein, q is 0, 1, 2, 3 or 4.

[0244] 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.

[0245] In some embodiments, q is selected from the compounds described herein.MF-363534227Attorney Docket No.: 18395-20370.40

[0246] In some embodiments, LBM isIn some embodiments, LBM is some embodiments,LBM is In some embodiments, LBM issome embodiments, IBM is In some embodiments, LBM isIn some embodiments, LBM isMF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, LBM is. In some embodiments, LBM is In some embodiments, LBM isIn some embodiments, LBM issome embodiments,LBM is In some embodiments, LBM isMF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, LBM issome embodiments,LBM is In some embodiments, LBM is. In someIn some embodiments, LBM is MF-363534227Attorney Docket No.: 18395-20370.40some embodiments, LBM isIn some embodiments, LBM isIn some embodiments, LBM issome embodiments,LBM is, In some embodiments, LBM isembodiments, LBM is In some embodiments, LBM is124MF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, LBM is. In some embodiments, LBM is In some embodiments, LBM is. In some embodiments, LBM is. In some embodiments, LBM is. In some embodiments, LBM is. In some embodiments, LBM is embodiments,LBM is In some embodiments, LBM isembodiments, LBM is In some embodiments, LBM is125MF-363534227Attorney Docket No.: 18395-20370.40embodiments,LBM is In some embodiments, LBM is. In some embodiments, LBM is. In someembodiments,LBM is In some embodiments, LBM isIn some embodiments, LBM is. In some Oembodiments,LBM is In some embodiments, LBM isIn some embodiments, LBM is. In someIn some embodiments, LBM isembodiments,LBM is In some embodiments, LBM isMF-363534227Attorney Docket No.: 18395-20370.40embodiments,LBM is In some embodiments, LBM isIn some embodiments, LBM is127MF-363534227Attorney Docket No.: 18395-20370.40 embodiments,LBM is In some embodiments, LBM isIn some embodiments, LBM is In some. In some. In some embodiments,LBM is In some embodiments, LBM isMF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, LBM isIn some embodiments, LBM isIn some embodiments, LBM isIn some embodiments, LBM is 129MF-363534227Attorney Docket No.: 18395-20370.40embodiments,LBM is In some embodiments, LBM isembodiments, LBM is

[0247] In some embodiments, LBM is selected from the compounds described herein.

[0248] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula Loo-1, Loo-2, Loo-3, Loo-4, Loo-5, Loo-6, Loo-7, Loo-8, Loo-9, or Loo- 10 respectively:130MF-363534227Attorney Docket No.: 18395-20370.40!-< H>-7 or a compound of formula l-oo’-l, l-oo’-2, l-oo’-3, I-oo’-4, I-oo’-5, 1-oo’-6, 1-oo’-7, 1-oo’-8, l-oo’-9, or I-oo’-lO respectively:131MF-363534227Attorney Docket No.: 18395-20370.40 l-oo -9 I-oo'-W or a compound of formula I-oo”-l, I-oo”-2, 1-oo”-3, 1-oo”-4, 1-oo”-5, 1-oo”-6, 1-oo”-7, 1-oo”-8, 1-oo”-9, or I-oo”-10 respectively:132MF-363534227Attorney Docket No.: 18395-20370.40l-eo'LlOor a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and 8described in embodiments herein, and wherein each of the variables, X, X1, x2. Y, Ri, R3, R3’, R4, Rs, t, m and n is as defined and described in WO 2017 / 007612 and WO 2018 / 0134684, the entirety of each of which is herein incorporated by reference.

[0249] Accordingly in some embodiments, the present invention provides a compound of formula l-oo-l, l-oo-2, 1-oo-3, 1-oo-4, 1-oo-5, 1-00-6, I-oo-7, 1-00-8, 1-oo-9, 1-oo-lO, I-oo'-l, I-oo'-2, I-oo'-3, 1-oo'- 4, I-oo'-5, l-oo'-6, I-oo'-7, I-oo'-8, l-oo'-9, I-oo'-lO, I-oo"-l, I-oo"-2, 1- oo"-3, 1-oo"-4, 1-oo"-5, 1-oo"- 6, 1-oo"-7, 1-oo"-8, 1-oo"-9, or I-oo"-10, or a pharmaceutically acceptable salt thereof, wherein:OY is a bond, Yi, O, NH, NR2, C(O)O, OC(O), C(O)NR2’, NR2’C(O), Yi— O, Yi— NH, Yi— NR2, YJ— C(O), YI— C(O)O, YI— OC(O), YJ— C(O)NR2’, or Yi— NR2'C(O), wherein Yj is Ci-Ce alkylene, C2-Ce alkenylene, or C2-Ce alkynylene; X is C(O) or C(R?)2; Xi-X2is C(R3)=N or C(R3)2---C(R3)2; each Ri is independently halogen, nitro, NH2, OH, C(O)OH, C1-C6 alkyl, or Ci-Ce alkoxy; R2is Ci-Ce alkyl, C2-Ce alkenyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C(O) — Ci-C& alkyl, C(O) — C2-Ce alkenyl, C(O) — C3- Cs cycloalkyl, or C(O)-3- to 8-membered heterocycloalkyl, and R2is optionally substituted with one or more of halogen, N(Ra)2, NHC(O)Ra, NHC(O)ORa, ORb, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, Cs-Cio aryl, or 5- to 10-membered heteroaryl, wherein each of the C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, Ce-Cio aryl or 5- to 10- membered133MF-363534227Attorney Docket No.: 18395-20370.40heteroaryl is optionally further substituted with one or more of halogen, NH2, CN, nitro, OH, C(O)OH, Cj-Cfi alkyl, Cj-Cs haloalkyl, Ci-Ce alkoxy, or Ci-Cc, haloalkoxy;R2' is H, Ci-Ce alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl, and R2', when not being H, is optionally substituted with one or more of halogen, N(Ra)2, NHC(O)Ra, NHC(O)ORa, ORb, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, Ce-C10 aryl, or 5- to 10- membered heteroaryl, wherein each of the C3-C8 cycloalkyl, 3- to 8- membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl is optionally further substituted with one or more of halogen, NH2, CN, nitro, OH, C(O)OH, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce alkoxy, or Ci- C haloalkoxy; each R3 is independently H or C1-C3 alkyl optionally substituted with Ce-Cio aryl or 5- to 10-membered heteroaryl; each R3' is independently C1-C3 alkyl; each R4 is independently H or C1-C3 alkyl; or two R4, together with the carbon atom to which they are attached, form C(O), a C3-C6 carbocycle, or a 4-, 5-, or 6-membered heterocycle comprising 1 or 2 heteroatoms selected from N and O; Rs is H, C1-C3 alkyl, F, or Cl; each Ra independently is H or Ci-Ce alkyl; Rb is H or tosyl; t is 0 or 1; m is 0, 1, 2 or 3; and n is 0, 1 or 2,

[0250] In some embodiments,LBM is ®. In some embodiments, LBMIn some embodiments,LBM is In some embodiments, LBM is134MF-363534227Attorney Docket No.: 18395-20370.40In some embodiments, LBM isIn some embodiments, LBM is135MF-363534227Attorney Docket No.: 18395-20370.40

[0251] In some embodiments, LBM is selected from the compounds described herein.

[0252] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-uu:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: A represents a monocyclic or bicyclic aromatic ring which may be substituted; B represents a six-membered unsaturated hydrocarbon ring or a six-membered unsaturated heterocycle containing one nitrogen atom as the heteroatom, each of which may be substituted; C represents a five-membered heterocycle containing one or two nitrogen atoms which may be substituted; W represents a single bond or a group represented by formula -CH:::CH-, X represents a group represented by formula -NQl1)- or oxygen, Y represents carbon or nitrogen; Z represents a group represented by¬ formula -N(R2)- or nitrogen; and R1and R2may be the same or different from each other and each represent hydrogen or lower alkyl; or the variables are as described and defined in US 5,721,246, the entirety' of each of which is herein incorporated by reference.

[0253] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-vv:136MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein each of the variables Ri, R2, and n is as described and defined in WO 2019 / 043214, the entirety of each of which is herein incorporated by reference.

[0254] 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-KB activation, and TNFa- Dependent Apoptosis, Cell, 2007, 131(4): 669-81, such as, for example:wherein 1is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom.

[0255] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a MDM2 (i.e. human double minute 2 or IIDM2) E3 ligase binding moiety thereby forming a compound of formula I-aaa- 1, 1-aaa-2, 1-aaa-3, 1-aaa-4, 1-aaa-5, 1-aaa-6, 1-aaa-7, 1-aaa-8, 1-aaa-9, 1- aaa-10, I-aaa- 11, 1-aaa-12, 1-aaa-13, 1-aaa-14, 1-aaa-15, 1-aaa-16, I-aaa- 17, or I-aaa- 18 respectively:137MF-363534227Attorney Docket No.: 18395-20370.40R3I-aaa-2M«»>5 t«a#4I~aaa~8S'5'I sias SQ138MF-363534227Attorney Docket No.: 18395-20370.40l-aas-H:-;ssa-£3I-sma-JS I £6139MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: X is selected from -CR2-, -O-, -S-, -S(O)-, - S(O)2-, and -NR-; each R is independently hydrogen or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 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, 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 heteroaiyl ring having 0-3 heteroatoms, 111 addition to the atom from which they are attached, independently selected from nitrogen, oxygen, and sulfur; Y and Z are independently selected from -CR= and -N=, Ring W is fused ring selected from benzo and a 5-6 membered heteroaryl with 1 -4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Rland R2are independently an optionally substituted monocyclic or bicyclic ring selected from phenyl, a 5-10 membered aryl, and a 5-10 membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R3and R4are independently selected from hydrogen and C1-6 alkyl,R5is selected from an optionally substituted monocyclic or bicyclic ring selected from phenyl, a 5-10 membered aryl, and a 5-10 membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, R6is selected from hydrogen, -C(O)R, -C(O)OR, and -C(O)NR2; R7is selected from hydrogen and RA; each RAis independently an optionally substituted group selected from Ci-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; R8is selected from -C(O)R and RA;R9is a mono-, bis-, or tri -substituent on Ring W, wherein each of the substituents are independently selected from halogen and an optionally substituted Ci-6 aliphatic; R10is selected from an optionally substituted monocyclic or bicyclic ring selected from phenyl, a 5- 10 membered aryl, and a 5-10 membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, R11is -C(O)OR or -C(O)NR2; R12and R1Jare independently selected from hydrogen and RA, or: R12and R13are optionally taken together with their intervening atoms to form an optionally substituted 3-8 membered saturated, partially unsaturated, carbocyclic or heterocyclic ring having 1-3 heteroatoms140MF-363534227Attorney Docket No.: 18395-20370.40independently selected from nitrogen, oxygen, and sulfur; R14is RA, R15is -CN; R16is selected from RA, -OR, -(CR2)o-6-C(0)R, -(CR2)o-6-C(0)OR, -(CR2)o-6-C(0)NR2, -(CR2)o-6-S(O)2R, - (CR2)O-6-N(R)S(0)2R, -(CR2)O-6-S(0)2NR2; R1' is selected from -(CR2)o-6-C(0)NR2; R18and R19are independently selected from hydrogen and RA; R20and R21are independently selected from hydrogen, RA, halogen, and -OR, or: R20and R21are optionally taken together with their intervening atoms to form a fused 5-7 membered partially unsaturated carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a fused 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R22, R23, R23, and R27are independently selected from hydrogen, RA, halogen, -C(O)R, -C(O)OR, - C(O)NR2, -NR2, -OR, -S(O)R, -S(O)2R, -S(O)2NR2; R24, R26, and R28are independently selected from hydrogen, RA, -C(O)R, -C(O)OR, - C(O)NR2, -S(O)R, -S(O)2R, and -S(O)2NR2; R1and R2are independently selected from halogen, -C=CR, -CN, -CFs, and -NO2; R3is -OR; R4, R3, R6are independently selected from hydrogen, halogen, RA, -CN, -CF3, -NR2, -OR, -SR, and -S(O)2R; R7IS a mono-, bis-, or tn-substituent, wherein each of the substituents are mdependenly selected from halogen; R8is a mono-, bis-, or tn-substituent, wherein each of the substituents are independently selected from hydrogen, halogen, RA, -CN, -C==CR, -NO2, and -OR; R9is RA; Z1is selected from hydrogen, halogen, and -OR; R10and R11are independently selected from hydrogen and RA; R12is selected from -C(O)R, -C(O)OR, - C(O)NR2, -OR, -S(O)2R, -S(O)2NR2, and -S(O)R; and R1is selected from hydrogen and RA.

[0256] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a MDM2 (i.e. human double minute 2 or HDM2) E3 ligase binding moiety thereby forming a compound of formula I-aaa-19, l-aaa-20, or l-aaa-21 respectively20141MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: R1is selected from hydrogen and RA; each RAis independently an optionally substituted group selected from Ci-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, R10is selected from an optionally substituted monocyclic or bicyclic ring selected from phenyl, a 5 - 10 membered aryl, and a 5-10 membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R12 and R13 are each independently selected from hydrogen and RA, or: R12and R13are optionally taken together with their intervening atoms to form an optionally substituted 4-8 membered saturated, partially unsaturated, carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, A5is selected from -C(R18a)= and -N=; A6is selected from -C(R,8b)= and -N=; A7is selected from -C(R18d)= and -N=; R18a, R18b, R18c, and R18dare each independently selected from hydrogen, halogen, RA, and -OR;each R is independently hydrogen or an optionally substituted group selected from Cn 6 aliphatic, phenyl, a 4-7 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; Ring W is an optionally substituted fused ring selected from benzo and a 5-6 membered heteroaiyl with 1- 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; and Q1is and optionally substituted bivalent group selected from alkylenyl, phenylenyl, heteroarylenyl, cycloalkylenyl, and heterocyclenyl.

[0257] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an IAP E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-bbb-1, 1- bbb-2, 1-bbb-3, or I-bbb-4 respectively:142MF-363534227Attorney Docket No.: 18395-20370.40{■ -.5 l--bhfe.-4or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: R1is selected from the group of H and alkyl; R2is selected from the group of H and alkyl; R3is selected from the group of H, alkyl, cycloalkyd and heterocycloalkyl; R4is selected from alkyl, cycloalkyd, heterocycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, further optionally substituted with 1-3 substituents selected from halogen, alkyl, haloalkyl, hydroxyl, alkoxy, cyano, (hetero)cycloalkyl or (hetero)aryl, or - C(O)NH-R4, where R4is selected from alkyl, cycloalkyl, heterocycloalkyl, cycloalkydal kyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroaryl alkyl, further optionally substituted with 1-3 substituents as described above; R5and R6are independently selected from the group of H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or fused rings, and R7is selected from the group of cycloalkyd, cycloalkylalkyl, heterocycloalkyl, heterocycloalkydalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyd, each one further optionally substituted with 1-3 substituents selected from halogen, alkyl, haloalkyl, hydroxyl, alkoxy, cyano, (hetero)cycloalkyl or (hetero)aryl, or -C(O)NH-R4, where R4is selected from alkyd, cycloalkyl, heterocycloalkyd, cycloalkylalkyl, heterocycloalkylalkyl, aryl, arylalkyd, heteroaryl, heteroarylalkyl, further optionally substituted with 1-3 substituents as described above, or the variables are as defined and described in WO 2017 / 011590 and US 2017 / 0037004, the entirety of each of whi ch is herein incorporated by reference.

[0258] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an E3 ubiquitin ligase (cereblon) binding moiety, a DCAF15 E3 ubiquitin ligase binding moiety, or a VHL E3 ubiquitin ligase binding moiety7, thereby forming a compound of formula I-ccc-1, 1-ccc-2, or I-ccc-3:143MF-363534227Attorney Docket No.: 18395-20370.40i-ecc -Aor a pharmaceutically acceptable salt thereof, wherein L and SBM is as defined above and described in embodiments herein, and wherein: each of X1, X2a, and X3ais independently a.... A bivalent moiety selected from a covalent bond,CH2, -C(O) - ’ ', each of X4aand X5ais independently a bivalent moiety selected from -CH2-, -C(O)-, ~C(S)~, or; R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or an optionally substituted C1-4 aliphatic; each of R2, R3b, and R4ais 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, R5ais hydrogen or C1-6 aliphatic;each R6is independently an optionally substituted group selected from C1-6 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 Aais 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; Ring Bais selected from 6-membered aryl containing 0-2 nitrogen atoms or a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or144MF-363534227Attorney Docket No.: 18395-20370.40sulfur; Ring Cais a selected from 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; m is 0, 1, 2, 3 or 4, o is 0, 1, 2, 3 or 4; q is 0, 1, 2, 3 or 4; and each R is independently hydrogen, or an optionally substituted group selected from Ci-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.

[0259] 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-ccc'-l or I-ccc"-l:or a pharmaceutically acceptable salt thereof, wherein SBM, L, Ring Aa, X1, X2a, X3a, R1, R2and m are as described above.

[0260] As defined above and described herein, each of X1, X2a, and Xjais independentlya bivalent moiety selected from a covalent bond, -CH2-, -C(O)-, -C(S)-, or

[0261] In some embodiments, X1is a covalent bond, CH?, -C(O) -, --C(S)--, or

[0262] In some embodiments, X1is selected from the compounds described herein.145MF-363534227Attorney Docket No.: 18395-20370.40

[0263] In some embodiments, X2ais a covalent bond, -CH2-, -C(O)-, -C(S)-, or

[0264] In some embodiments, X2ais selected from the compounds described herein.

[0265] In some embodiments, Xjais a covalent bond, -CH2-, -C(O)-, -C(S)-, or

[0266] In some embodiments, Xjais selected from the compounds described herein.

[0267] As defined above and described herein, each of X4and X5is independently a Obivalent moiety selected from -CH2-, -C(O)-, -C(S)-, or?.

[0268] In some embodiments X4ais a covalent bond, -CH2-, -C(O)-, -C(S)~, or

[0269] In some embodiments X4ais selected from the compounds described herein.

[0270] In some embodiments X5ais a covalent bond, CH2 -C(O) -, --C(S) or

[0271] In some embodiments X5ais selected from the compounds described herein.

[0272] As defined above and described herein, R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, S(O)2R, -NR2, or an optionally substituted C1-4 aliphatic.

[0273] In some embodiments, R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or an optionally substituted C1-4 aliphatic.

[0274] In some embodiments, R1is selected from the compounds described herein.146MF-363534227Attorney Docket No.: 18395-20370.40

[0275] As defined above and described herein, each of R2, R3b, and R4ais 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(0)NR2, or-N(R)S(O)2R.

[0276] In some embodiments, R2is 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.

[0277] In some embodiments, R2is selected from the compounds described herein.

[0278] In some embodiments, R3bis 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.

[0279] In some embodiments, R3bis methyl.

[0280] In some embodiments, R3bis selected from the compounds described herein.

[0281] In some embodiments, R4ais 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.

[0282] In some embodiments, R4ais methyl.

[0283] In some embodiments, R4ais selected from the compounds described herein.

[0284] As defined above and described herein, R5ais hydrogen or C1-6 aliphatic.

[0285] In some embodiments, R5ais t-butyl.

[0286] In some embodiments, R5ais selected from the compounds described herein.

[0287] As defined above and described herein, each R6is independently an optionally substituted group selected from C1-6 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.147MF-363534227Attorney Docket No.: 18395-20370.40

[0288] In some embodiments, R6is an optionally substituted Ci-6 aliphatic group. In some embodiments, R6is an optionally substituted phenyl. In some embodiments, R6is 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, R6is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0289] In some embodiments, R6is selected from the compounds described herein.

[0290] As defined above and described herein, Ring Aais 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.

[0291] In some embodiments Ring Aais a fused 6-membered aryl containing 0-2 nitrogen atoms. In some embodiments Ring Aais a fused 5 to 7-membered partially saturated carbocyclyl. In some embodiments Ring Aais a fused 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur. In some embodiments Ring Aais a fused 5- membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0292] In some embodiments. Ring Aais a fused phenyl.

[0293] In some embodiments. Ring Aais selected from the compounds described herein.

[0294] As defined above and described herein, Ring Bais selected from 6-membered aryl containing 0-2 nitrogen atoms or a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0295] In some embodiments, Ring Bais a 6-membered aiyl containing 0-2 nitrogen atoms. In some embodiments, Ring Bais a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.148MF-363534227Attorney Docket No.: 18395-20370.40

[0296] In some embodiments, RingBais,

[0297] In some embodiments, Ring Bais selected from the compounds described herein.

[0298] As defined above and described herein, Ring Cais selected from 6-membered aiyl containing 0-2 nitrogen atoms or a 5 -membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0299] In some embodiments. Ring Cais a 6-membered aryl containing 0-2 nitrogen atoms. In some embodiments, Ring Cais a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0300] In some embodiments. RingCais

[0301] In some embodiments. Ring Cai the compounds described herein.

[0302] As defined above and described herein, m is 0, 1, 2, 3 or 4.

[0303] 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.

[0304] In some embodiments, m is selected from the compounds described herein.

[0305] In some embodiments, o is selected from the compounds described herein.

[0306] As defined above and described herein, o is 0, 1, 2, 3 or 4.

[0307] In some embodiments, o is 0. In some embodiments, o is 1. In some embodiments, o is 2. In some embodiments, o is 3. In some embodiments, o is 4.

[0308] In some embodiments, o is selected from the compounds described herein.

[0309] As defined above and described herein, q is 0, 1, 2, 3 or 4.149MF-363534227Attorney Docket No.: 18395-20370.40

[0310] 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.

[0311] In some embodiments, q is selected from the compounds described herein.

[0312] As defined above and described herein, each R is independently hydrogen, or an optionally substituted group selected from Ci-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, m addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.

[0313] 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.

[0314] In some embodiments, R is selected from the compounds described herein,

[0315] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a VEIL, E13 ubiquitin ligase binding moiety, thereby forming a compound of formula I-ddd:150MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM is as defined above and described in embodiments herein, and wherein: X is -C(O)-, -C(O)NR-, -SO2-, -SO2NR-, or an optionally substituted 5-membered heterocyclic ring; X1is a bivalent group selected from a covalent bond, -O-, -C(O)-, -C(S)-, -C(R)2-, -NR-, -S(O)-, or -SO2-; X2is an optionally substituted bivalent group selected from C1-6 saturated or unsaturated alkylene, phenylenyl, a 5-6 membered heteroarylenyl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclylenyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R1is RA, -C(R)2RA, -OR, -SR, -N(R)2, -C(R)2OR, -C(R)2N(R)2, -C(R)2NRC(O)R, - C(R)2NRC(O)N(R)2, - NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, or -NRSO2R; each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 3-7 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, or: two R groups on the same atom are optionally taken together with their intervening atoms to form an optionally substituted 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicy lie, or spirocyclic carbocyclic ring or heterocyclic ring with 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;RAis an optionally substituted group selected from C1-6 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;R2is hydrogen, halogen, -CN,Ring A is a ring selected from phenyl, a 5-6 membered heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4 to 9-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur,each of R3is independently hydrogen, halogen, Cnealkyl, Ci-6haloalkyl, -CN, -NO2, -OR, -SR, -N(R)2, - SI(R)3, -SO2R, -SO2N(R)2, -S(O)R, -C(O)R, -C(O)OR, -C(O)N(R)2, - 151MF-363534227Attorney Docket No.: 18395-20370.40C(O)N(R)OR, -C(R)2NRC(O)R, -C(R)2NRC(O)N(R)2, -OC(O)R, -OC(O)N(R)2, -OP(O)(R)2, -OP(O)(OR)2, - OP(O)(OR)N(R)2, -OP(O)(N(R)2)2-, -N(R)C(O)OR, -N(R)C(O)R, - NRC(O)N(R)2, -N(R)SO2R, - NP(O)(R)2, -N(R)P(O)(OR)2J-N(R)P(O)(OR)N(R)2, - N(R)P(O)(N(R)2)2, -N(R)SO2R, orRA;or two R3groups are optionally taken together to form an optionally substituted 5-7 membered partially unsaturated or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, R4is hydrogen, -C(O)R, -C(O)OR, -C(O)NR2, - P(O)R2, -P(O)(OR)2, -(CR2)1-3OP(O)R2, -(CR2)I-3OP(O)(OR)2, or RA; n is 0, 1, 2, 4, or 5.

[0316] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is an IAP binding moiety thereby forming a compound of formula I-fff:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: W is selected from H and lower alkyl that optionally may be substituted with 1-3 deuterium atoms; Y is lower alkyl that optionally may be substituted with OR6; R1, R2and R3are the same or different and each is independently selected from H and cyano; R4is lower alkyl; R5is selected from the group a) lower alkyl that optionally may be substituted with SO2R6and OR6, b) heterocyclyl, and c) aryl that optionally may be substituted with C(O)R', halo and cyano; Z is selected from the group a) aryl that optionally may be substituted with lower alkyl, OR6, halogen and aryl that optionally may be substituted with halogen, b) heteroaryl that optionally may be substituted with lower alkyl, cycloalkyl, OR6, halogen, oxo and aryl that optionally may substituted with cyano, and c) aryl fused with heterocyclyl, wherein the aryl optionally may be substituted with OR6and halogen, and the heterocyclyl optionally may be substituted with oxo, and d) heterocyclyl; R6is selected from H and lower alkyl that optionally may be substituted with halogen and deuterium, and R7is lower alkyl, or the variables are as described and defined in WO152MF-363534227Attorney Docket No.: 18395-20370.402014 / 044622, US 2015 / 0225449, WO 2015 / 071393, and US 2016 / 0272596, the entirety of each of which is herein incorporated by reference.

[0317] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a MDM2 binding moiety thereby forming a compound of formula I-ggg:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, as described and defined in Hines, J. et al., Cancer Res. (DOI: 10.1158 / 0008- 5472. CAN- 18-2918), the entirety of each ofwhich is herein incorporated by reference.

[0318] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a DCAF 16 binding moiety thereby forming a compound of formula I-hhh:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described m embodiments herein, 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.

[0319] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a RNF114 binding moiety thereby forming a compound of formula I-ni:153MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, as described and defined m Spradin, J. N. et al., bioRxiv (doi: https: / / doi.org / 10.1101 / 436998), the entirety of each of which is herein incorporated by reference.

[0320] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a RNF4 binding moiety thereby forming a compound of formula I-jjj:J jjJor a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, 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.

[0321] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a E3 ubiquitin ligase (cereblon) binding moiety thereby forming a compound of formula I-ppp-1, 1-ppp-2, 1-ppp-3, or I-ppp-4:154MF-363534227Attorney Docket No.: 18395-20370.40or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described herein, and wherein each of the variables R4, R10, R11, R15, Rl°, R17, W1, W2, and X is as defined in WO 2019 / 099868 which is herein incorporated by reference in its entirety, and where is attached to R17or R16at the site of attachment of R12as defined m WO2018 / 237026, such thatKtakes the place of the R12substituent.

[0322] In some embodiments,LBM is. In someembodiments, LBM is155MF-363534227Attorney Docket No.: 18395-20370.40embodiments,LBM is 0^. In some embodiments,LBM is. In some embodiments,LBM is In some embodiments, LBM is156MF-363534227Attorney Docket No.: 18395-20370.40 embodiments,LBM is In some embodiments, LBM is157MF-363534227Attorney Docket No.: 18395-20370.40 embodiments,LBM is In some embodiments, LBM isembodiments,LBM is In some embodiments, LBM is158MF-363534227Attorney Docket No.: 18395-20370.40embodiments, LBM isIn some embodiments, LBM isIn some embodiments, LBM isembodiments,LBM is In some embodiments, LBM is 159MF-363534227Attorney Docket No.: 18395-20370.40TO In some embodiments, LBM is In some embodiments,LBM is In some embodiments, LBM isHO In some embodiments, LBM is In some embodiments,LBM is HO In some embodiments, LBM isHO. In some embodiments, LBM is HO In some embodiments,LBM is In some embodiments, LBM isIn some embodiments,LBM is In some embodiments, LBM is. In some embodiments, LBM is 160MF-363534227Attorney Docket No.: 18395-20370.40 In some embodiments,LBM is. In some embodiments, LBM isIn some embodiments, LBM isIn some embodiments, LBM issome embodiments,LBM isz. In some embodiments, LBM is161MF-363534227Attorney Docket No.: 18395-20370.40. In some embodiments,LBM is In some embodiments, LBM isIn some embodiments,In some embodiments, LBM is162MF-363534227Attorney Docket No.: 18395-20370.40some embodiments, LBM issome embodiments, LBM is. In some embodiments, LBM is163MF-363534227Attorney Docket No.: 18395-20370.40

[0323] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-qqq:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, wherein: each X1is independently-CH2-, -O-, -NR-, -CF-,X2and X3are independently -CH2-, -C(O)-, -C(S)-, or Z1and Z2are 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; L1is 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 R1is independently selected from hydrogen, deuterium, R4, halogen, -CN, -NO2, -OR, - SR, -NR2, -S(O)2R, - S(O)2NR2, -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 R1groups 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;164MF-363534227Attorney Docket No.: 18395-20370.40each R is independently selected from hydrogen, or an optionally substituted group selected from Ci-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;R2is selected fromor 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 R3is 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 R4is independently selected from an optionally substituted group selected from C1-6aliphatic, 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.

[0324] As defined above and described herein each X1is independently a covalent bond,O-CH2-, -O-, -NR-, -CF2-,?, -C(O)-, -C(S)-, or%’A.165MF-363534227Attorney Docket No.: 18395-20370.40

[0325] In some embodiments, X1is a covalent bond. In some embodiments, X1is -CH2-. In some embodiments, X1is -O-, In some embodiments, X1is -NR-. In some embodiments,X1is -CF2-. In some embodiments, X1is. In some embodiments, X1is -C(O)-. In Asome embodiments, X1is -C(S)-. In some embodiments, X1is*.

[0326] In certain embodiments, X4is selected from those of the compounds described herein.

[0327] As defined above and described herein, X2and X3are independently -CH2-, - 0C(O)-, -C(S)-, or ".

[0328] In some embodiments, X2and X3are independently -CH2-. In some embodiments, X2and X3are independently -C(O)-. In some embodiments, X2and X3are independently - < >C(S)-. In some embodiments, X and X are independently.

[0329] In certain embodiments, X and X3are independently selected from those of the compounds described herein.

[0330] As defined above and described herein, X4is a covalent bond, -CH2-, -O-, -NR-, -CF2-, ^^^CfOE -CCS)-, or VV..

[0331] As defined above and described herein, Z1and Z2are independently a carbon atom or a nitrogen atom.

[0332] In some embodiments, Z1and Z2are independently a carbon atom. In some embodiments, Z1and Z2are independently a carbon atom.

[0333] In certain embodiments, Z1and Z2are independently selected from those of the compounds described herein.166MF-363534227Attorney Docket No.: 18395-20370.40

[0334] 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.

[0335] 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.

[0336] In certain embodiments, Ring A is selected from those of the compounds described herein.

[0337] As defined above and described herein, L1is 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-.

[0338] In some embodiments, L1is a covalent bond. In some embodiments, L1is 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-.

[0339] In some embodiments, L1is -C(O)-.

[0340] In certain embodiments, L1is selected from those of the compounds described herein.

[0341] As defined above and described herein, each R1is 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 R1groups 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.

[0342] In some embodiments, R1is hydrogen. In some embodiments, R1is deuterium. In some embodiments, R1is R4. In some embodiments, R1is halogen. In some embodiments,167MF-363534227Attorney Docket No.: 18395-20370.40R1is -CN. In some embodiments, R1is -NO2. In some embodiments, R1is -OR. In some embodiments, R1is -SR. In some embodiments, R1is -NR?. In some embodiments, R1is -S(O)2R In some embodiments, R1is -S(O)2NR2. In some embodiments, R1is -S(O)R. In some embodiments, R1is -CF2R. In some embodiments, R1is - CF3. In some embodiments, R1is -CR2(OR). In some embodiments, R1is -CR2(NR2). In some embodiments, R1is -C(O)R. In some embodiments, R1is -C(O)OR. In some embodiments, R1is - C(O)NR2. In some embodiments, R1is -C(O)N(R)OR. In some embodiments, R1is -OC(O)R. In some embodiments, R1is -OC(O)NR2. In some embodiments, R1is -C(S)NR2. In some embodiments, R1is - N(R)C(O)OR. In some embodiments, R1is -N(R)C(O)R. In some embodiments, R1is -N(R)C(O)NR2. In some embodiments, R1is -N(R)S(O)2R. In some embodiments, R1is -OP(O)R2. In some embodiments, R1is -OP(O)(OR)2, In some embodiments, R1is -OP(O)(OR)NR2 In some embodiments, R1is - OP(O)(NR2)2. In some embodiments, R1is -Si(OR)R2 In some embodiments, R1is -SiR3. In some embodiments, two R1groups 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.

[0343] In certain embodiments, each R1is independently selected from those of the compounds described herein.

[0344] As defined above and described herein, each R is independently selected from hydrogen, or an optionally substituted group selected from Ci-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.

[0345] 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 a 5-6 membered 168MF-363534227Attorney Docket No.: 18395-20370.40heteroaryl 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.M j- — ( g i — A

[0346] As defined above and described herein, R2is selected from N_zorhydrogen.- (R3)n

[0347] In some embodiment R2isjn someembodiments, R2is hydrogen.

[0348] In certain embodiments, R2is selected from those of the compounds described herein.

[0349] 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.

[0350] 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.

[0351] In certain embodiments, Ring B is selected from those of the compounds described herein.

[0352] As defined above and described herein, each R3is 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, - 169MF-363534227Attorney Docket No.: 18395-20370.40OC(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.

[0353] In some embodiments, R3is hydrogen. In some embodiments, R3is deuterium. In some embodiments, R3is R4. In some embodiments, R3is halogen. In some embodiments, R3is -CN. In some embodiments, R3is -NO2. In some embodiments, R3is -OR In some embodiments, R3is -SR. In some embodiments, R3is -NR2. In some embodiments, R3is -S(O)2R In some embodiments, R3is -S(O)2NR2. In some embodiments, R3is -S(O)R. In some embodiments, R3is -CF2R. In some embodiments, R3is - CF3. In some embodiments, R3is -CR2(OR). In some embodiments, R3is -CR2(NR2). In some embodiments, R3is - C(O)R In some embodiments, R3is -C(O)OR In some embodiments, R3is - C(O)NR2. In some embodiments, R3is -C(O)N(R)OR. In some embodiments, R3is -OC(O)R. In some embodiments, R3is -OC(O)NR2. In some embodiments, R3is -N(R)C(O)OR. In some embodiments, R3is -N(R)C(O)R. In some embodiments, R3is -N(R)C(O)NR2. In some embodiments, R3is -N(R)S(O)2R In some embodiments, R3is -OP(O)R2. In some embodiments, R3is -OP(O)(OR)2. In some embodiments, R3is -OP(O)(OR)NR2In some embodiments, R3is -OP(O)(NR2)2. In some embodiments, R3is -SiR3.

[0354] In certain embodiments, R3is selected from those of the compounds described herein,

[0355] As defined above and described herein, each R4is independently an optionally substituted group selected from C1-6 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.

[0356] In some embodiments, R4is an optionally substituted C1-6 aliphatic. In some embodiments, R4is an optionally substituted phenyl. In some embodiments, R4is 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, R4is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0357] In certain embodiments, R4is selected from those of the compounds described herein.170MF-363534227Attorney Docket No.: 18395-20370.40

[0358] As defined above and described herein, is a single or double bond.

[0359] In some embodiments, is a single bond. In some embodiments, is a double bond.

[0360] In certain embodiments, is selected from those of the compounds described herein.

[0361] As defined above and described herein, m is 0, 1, 2, 3 or 4.

[0362] 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.

[0363] In certain embodimen ts, m is selected from those of the compounds described herein.

[0364] As defined above and described herein, n is 0, 1, 2, 3 or 4.

[0365] 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.

[0366] In certain embodiments, n is selected from those of the compounds described herein.

[0367] As defined above and described herein, o is 0, 1, or 2.

[0368] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, m is 2.

[0369] In certain embodiments, o is selected from those of the compounds described herein.

[0370] In some embodiments, the present invention provides a compound of formula I-qqq, wherein Ring A is benzo, o is I, X1is -CH2-, X2and X3are -C(O)-, and Z1and Z2are carbon atoms as shown, to provide a compound of formula I-qqq-1:or a pharmaceutically acceptable salt thereof, wherein each of171MF-363534227Attorney Docket No.: 18395-20370.40SBM, L, L1, R1, R2, and m is as defined above and described in embodiments herein, both singly and in combination.

[0371] In some embodiments, the present invention provides a compound of formula I-qqq, wherein Ring A is benzo, o is 1, X1, X2and X3are -C(O)-, and Z1and Z2are carbonatoms as shown, to provide a compound of formula I-qqq-12: I-qqq-12or a pharmaceutically acceptable salt thereof, wherein each of SBM, L, L1, R1, R2, and m is as defined above and described m embodiments herein, both singly and in combination.

[0372] In some embodiments, LBM is. In some embodiments, LBM isIn some embodiments, LBM is In some embodiments,LBM is In some embodiments, LBM is In someOembodiments,LBM is In some embodiments,LBM issome embodiments,LBM is

[0373] In some embodiments, LBM is selected from the compounds described herein.172MF-363534227Attorney Docket No.: 18395-20370.40

[0374] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a RPN13 binding moiety thereby forming a compound of formula l-rrr.*~ror a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein: m each pair of A’s, one A is hydrogen, and the other A is one of: (i) phenyl, optionally substituted with 1-5 substituents selected from the group consisting of R1, OR1, NR’R2, S(O)qR1, SO2R1R2, NR1SO2R2, C(O)R1, C(O)OR1, CfO^R2, NR^ OjR2, NR1C(O)OR2, CF3, and OCF3,(ii) naphthyl, optionally substituted with 1-5 substituents selected from the group consisting of R1, OR1, NRTR2, SCOjqR1, SO^R2, NR^ChR2, COR1, C(0)0R1, C(0)NR1R2,NR1C(0)R2, NR1C(0)0R2, CF3, and 0CF3;(iii) a 5 or 6 membered monocyclic heteroaryl group, having 1 -3 heteroatoms selected from the group consisting of O, N, and S, optionally substituted with 1-3 substituents selected from the group consisting of R1, OR1, NR1R2, S(O)qR1, SO^R2, NRISO2R2, C(0)R’, C(0)0R1, C(O)NR1R2, NR1C(0)R2, NR1C(0)0R2, CF3, and 0CF3;and (iv) an 8 to 10 membered bicyclic heteroallyl group containing 1-3 heteroatoms selected from the group consisting of O, N, and S, and the second ring is fused to the first ring using 3 to 4 carbon atoms, and the bicyclic hetero aryl group is optionally substituted with 1-3 substituents selected from the group consisting of R1, OR1, R!R2, S02R!R2, NRJS02R2, C(0)R1, C(O)OR1, C(0)NR!R2, NR‘C(0)R2, NR1C(0)0R2, CF3, and OCF3;wherein Y is selected from the group consisting of O, S, NR1and CR'RZ,wherein R1and R2are selected from the group consisting of hydrogen, nitro, hydroxyl, carboxy, amino, halogen, cyano and C1-C14 linear or branched alkyl groups, that are optionally substituted with 1-3 substituents selected from the group consisting of C1-C14173MF-363534227Attorney Docket No.: 18395-20370.40linear or branched alkyl, up to perhalo substituted C1-C14 linear or branched alkyl, C1-C14 alkoxy, hydrogen, nitro, hydroxyl, carboxy, amino. Ct-Cj4 alkylamino, C1-C14 dialkylamino, halogen, and cyano;and wherein Z is selected from the group consisting of hydrogen; C1-C14 linear, branched, or cyclic alkyls; phenyl, benzyl, 1-5 substituted benzyl, Ci to C3 alkyl-phenyl, wherein the alkyl moiety is optionally substituted with halogen up to perhalo; up to perhalo substituted C1-C14 linear or branched alkyls; -(CH2)q-K, where K is a 5 or 6 membered monocyclic heterocyclic ring, containing 1 to 4 atoms selected from oxygen, nitrogen and sulfur, which is saturated, partially saturated, or aromatic, or an 8 to 10 membered bicyclic heteroaryl having 1-4 heteroatoms selected from the group consisting of O, N, and S, wherein said alkyl moiety is optionally substituted with halogen up to perhalo, and wherein the variable q is an integer ranging from 0 to 4, or the variables are as described and defined in WO 2019 / 165229, the entirety of each of which is herein incorporated by reference.

[0375] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a Ubr 1 binding moiety as described in Shanmugasundaram, K. et al, J. Bio. Chem. 2019, doi: 10.1074 / jbc. ACl 19.010790, the entirely' of each of which is herein incorporated by reference, thereby forming a compound of formula I-sss-1 or I-sss-2:I-sss-l I-sss-2or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein.

[0376] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is a CRBN E3 ubiquitin ligase binding moiety thereby forming a compound of formula I-uuu-1, 1- uuu-2, 1-uuu-3 or I-uuu-4:174MF-363534227Attorney Docket No.: 18395-20370.40I-ttt-1I-ttt-3 I-ttt-4or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein:Y is NH or CH2;A1is selected from the group consisting of aryl and aryl substituted with R1;A3is selected from the group consisting of heteroaryl and heteroaryl substituted with R2, R1is selected from the group consisting of: -C(=O)-O-Ci-6-alkyl, -COOH, -NH-(C=O)-CI-6-alkyl, -NH2, and -NO2; R2is selected from the group consisting of: -COOH, -C(=O)-O-Ci-6- alkyi, -NH2, and -NO2; or the variables are as described and defined m WO 2019 / 236483, the entirety of each of which is herein incorporated by reference.

[0377] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is human kelch-like ECH-associated protein 1 (KEAP1) thereby forming a compound of formula I- vvv:I-vvvor a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, both singly and in combination.175MF-363534227Attorney Docket No.: 18395-20370.40

[0378] In certain embodiments, the present invention provides a compound of Formula A, 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-www:I -WWWor a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, both singly and in combination.

[0379] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is KEAP1-NRF2 binding moiety thereby forming a compound of formula I-xxx or I-xxx-2:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, and wherein:i 6GOj. ^4 ' 1 R is methyl or halo;R1is R is methyl or R3is H; R4is H or halo; R3is methoxy or H; R6is H or methyl; R8is H, methyl or ethyl;176MF-363534227Attorney Docket No.: 18395-20370.40or the variables are as described and defined m WO 2020 / 018788, the entirety of each of which is herein incorporated by reference.

[0380] In certain embodiments, the present invention provides a compound of Formula A, 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-yyy- 1 or I-yyy-2:or a pharmaceutically acceptable salt thereof, wherein L and SBM are as defined above and described in embodiments herein, both singly and in combination.

[0381] In some embodiments,LBM isembodiments,LBM is

[0382] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is DCAF1 binding moiety thereby forming a compound of formula I-dddd:i-dddor apharmaceutically acceptable salt thereof, wherein:MF-363534227Attorney Docket No.: 18395-20370.40Ring L is phenyl, a 4-7 membered partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1 -4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Ring F is phenylenyl, a 4-10 membered partially unsaturated carbocyclyienyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Y1is a Ci- 3 hydrocarbon chain wherein each methylene is optionally substituted with -CR2-, -CR(OR)-, - C(O)-, -C(NR)-, -C(NOR)-, -S(O)-, or -S(O)2-; Rais an optionally substituted Ci-6 aliphaticRing G is phenyl, a 5-7 membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Rbis hydrogen, an optionally substituted C1-6 aliphatic, phenyl, or a 5-6 membered heteroaiyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or: Raand Rbare optionally taken together with their intervening atoms to form an optionally substituted 9-10 membered saturated or partially unsaturated bicyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, orwhen Y1is -C(NR)-, Rbis optionally taken together with R of -C(NR)- with their intervening atoms to form a 5-7 membered partially unsaturated heterocyclyl with 0-1 heteroatoms, m addition to the 2 nitrogen atoms within the heterocyclyl, independently selected from nitrogen, oxygen, and sulfur;Rcis -CR2CONR2, a 5-7 membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Rdis hydrogen, or: when Rcis -CR2CONR2, Rdis optionally taken together with a single R of -CR2CONR2 with their intervening atoms to form a 5-7 membered saturated or partially unsaturated heterocyclyl with 0-3 heteroatoms, in addition to the nitrogen atom to which Rdis attached, independently selected from nitrogen, oxygen, and sulfur; Re, Rf, and Rgare each independently selected from hydrogen, oxo, RA, halogen, -CN, -NO2, -OR, - SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, - 178MF-363534227Attorney Docket No.: 18395-20370.40C(O)NROR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, -OP(O)(OR)NR2, -OP(O)(NR2)2, -NRC(O)OR, -NRC(O)R, -N C(O)N(R)2, -NRS(O)2R, -NP(O)R2, - NRP(O)(OR)2, -NRP(O)(OR)NR2J- NRP(O)(NR2)2, -P(O)R2, -P(O)(OR)2, -P(O)(OR)NR2, and -P(O)(NR2)2;eachAis independently an optionally substituted group selected from Ci-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 Cn 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, or:two R groups on the same atom are optionally taken together with their intervening atoms to form an optionally substituted 3-7 membered saturated or partially unsaturated ring having 0-3 heteroatoms, in addition to the atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur; s is 0 or 1, and each of e, f, and g are independently 0, 1, 2, 3, or 4; wherein said compound of formula I-dddd is optionally substituted withwherein is a warhead group.

[0383] In certain embodiments, the present invention provides a compound of Formula A, wherein LBM is DCAF1 binding moiety thereby forming a compound of formula I-eeee:or a pharmaceutically acceptable salt thereof, wherein:Ring H is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, Ring I is phenylenyl, a 3-11 membered saturated 179MF-363534227Attorney Docket No.: 18395-20370.40or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclylenyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Ring J is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclylenyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring K is phenyl, naphthyl, a 9-10 membered saturated or partially unsaturated bicyclic heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-13 membered monocyclic, bicyclic, or tricyclic heteroarylenyl with 1-5 heteroatoms independently selected from nitrogen, oxygen and sulfur; Rh, R1, R', and Rkare each independently selected from hydrogen, oxo, RA, halogen, -CN, -NO2, -OR, - SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, - C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2J-OP(O)R2, -OP(O)(OR)2, -OP(O)(OR)NR2, - OP(O)(NR2)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, -NRS(O)2R, -NP(O)R2, - NRP(O)(OR)2, -NRP(O)(OR)NR2, - NRP(O)(NR2)2, -P(O)R2, -P(O)(OR)2, -P(O)(OR)NR2, and -P(O)(NR2)2, or:an R1group on Ring I and an R* group or Ring J are optionally taken together with their intervening atoms to form a 5-8 membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;an R1group on Ring I and an R* group or Ring J are optionally taken together with their intervening atoms to form a 5-8 membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each RAis independently an optionally substituted group selected from Ci-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 Cn 6 aliphatic, phenyl, a 4-7 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, or: two R groups on the same atom are optionally taken together with their intervening atoms to form an optionally substituted 3-7 membered180MF-363534227Attorney Docket No.: 18395-20370.40saturated or partially unsaturated ring having 0-3 heteroatoms, in addition to the atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur; each of X1and X2is independently a covalent bond, spiro-fusion between the two rings that X1or X2connect, -CR2-, -CR(OR)-, -CRF-, -CF2-, -NR-, -O-, -S-, or -S(O)2-; s is 0 or 1; and each of w, x, y, and z are independently 0, 1, 2, 3, or 4;wherein said compound of formula I-eeee is optionally substituted withwherein is a warhead group.

[0384] As described above and defined herein, Ring E is phenyl, a 4-7 membered partially unsaturated carbocyclyl or heterocyclyl with 1 -3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0385] In some embodiments. Ring E is phenyl. In some embodiments, Ring E is a 4-7 membered partially unsaturated carbocyclyl. In some embodiments, Ring E is a 4-7 membered partially unsaturated heterocyclyl with 1 -3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1 -4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0386] In some embodiments, Ring E is cyclobutyl, azetidinyl, cyclohexyl, cyclohexenyl, tetrahydro- 2H-pyranyl, pyrrolidinyl, 4,5-dihydro-lH-pyrazolyl, piperidinyl, phenyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, indolyl, benzoimidazolyl, pyrazolo[l,5-a]pyridyl, or [1,2,4]triazolo[1,5-a]pyridyl.

[0387] In some embodiments, Ring E is as depicted in the compounds described herein.

[0388] As described above and defined herein. Ring F is phenylenyl, a 4-10 membered partially unsaturated carbocyclylenyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.181MF-363534227Attorney Docket No.: 18395-20370.40

[0389] In some embodiments, Ring F is phenylenyl. In some embodiments, Ring F is a 4-10 membered partially unsaturated carbocyclylenyl. In some embodiments. Ring F is a 4-10 membered partially unsaturated heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring F is a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1 -4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0390] In some embodiments, Ring F is cyclobutylenyl, azetinylenyl, cyclopentylenyl cyclohexyl, phenylenyl, pyrrolylenyl, imidazolylenyl, pyrazolylenyl, 1,2,3 -triazo lylenyl, 1, 2, 4-triazo lylenyl, pyridylenyl, indazolyl, 1,2,3,6-tetrahydropyridinyl, 4,5,6,7-tetrahydro-lH-pyrazolo[4,3-b]pyridyl, benzoimidazolyl, 3,4-dihydroquinolinyl, or 4,5,6,7-tetrahydro-lH-pyrazolo[4,3-c]pyridyl.

[0391] In some embodiments. Ring F is as depicted in the compounds described herein.

[0392] As described above and defined herein, Ring G is phenyl, a 5-7 membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0393] In some embodiments. Ring G is phenyl. In some embodiments. Ring G is a 5-7 membered saturated or partially unsaturated carbocyclyl. In some embodiments. Ring G is a 5-7 membered saturated or partially unsaturated heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring G is a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0394] In some embodiments. Ring G is cyclohexyl, cyclohexenyl, isothiazolyl, phenyl, or pyridyl.

[0395] In some embodiments. Ring G is as depicted in the compounds described herein.

[0396] As described above and defined herein, Ring H is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.182MF-363534227Attorney Docket No.: 18395-20370.40

[0397] In some embodiments, Ring H is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclyl. In some embodiments, Ring H is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0398] In some embodiments, Ring H is cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, cyclohexyl, piperidinyl, piperazinyl, 3,6-dihydro-2H-pyranyl, tetrahydro-2H-pyranyl, morpholinyl, piperazinyl, 2,7- diazaspiro[3.5]nonanyl, 3,4-dihydro-2H-pyrido[3,2-b][l,4]oxazinyl, 2-oxa-5-azabicyclo[2.2. l]heptanyl, 6- oxa-3-azabicyclo[3.1.1]heptanyl, or 2-oxa-5-azabicyclo[2.2.2]octanyl.

[0399] In some embodiments. Ring H is as depicted in the compounds described herein.

[0400] As described above and defined herein, Ring I is phenylenyl, a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclylenyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0401] In some embodiments. Ring I is phenylenyl. In some embodiments, Ring I is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclylenyl. In some embodiments, Ring I is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring I is a 5-9 membered monocyclic or bicyclic heteroarylenyl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0402] In some embodiments. Ring I is phenylenyl, imidazolylenyl, pyrazolylenyl, oxazolylenyl, thiazolylenyl, 1,2-thiazinanylenyl, pyridylenyl, pyridazinylenyl, pyrimidinylenyl, 2,6- diazaspiro[3.5]nonanylenyl, 2,3-dihy dro- lH-pyrrolo[2,3-b]pyridylenyl, 2,3-dihydro-lH-pyrrolo[3,2- c]pyridylenyl, lH-pyrrolo[2,3-b]pyridylenyl, 3H-imidazo[4,5-b]pyridylenyl, 9H-purinylenyl, 1,2,3, 4- tetrahydro-1, 8-naphthyridinylenyl, or 1,2,3,4-tetrahydro-1,6-naphthyridinylenyl.

[0403] In some embodiments, Ring I is as depicted in the compounds described herein.183MF-363534227Attorney Docket No.: 18395-20370.40

[0404] As described above and defined herein. Ring J is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclylenyl or heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0405] In some embodiments, Ring J is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclyl. In some embodiments, Ring J is a 3-11 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0406] In some embodiments, Ring J is cyclohexylenyl, azetidinylenyl, pyrrolidinylenyl, imidazolylenyl, piperidinylenly, piperazinylenyl, azepanylenyl, 8-azabicyclo[3.2.1]octanylenyl, 2- azabicyclop.2. l]octanylenyl, 2-azabicyclo[3.2.2]nonanylenyl, octahydro-1H-pyrrolo[3,2-b]pyridylenyl, decahydro-1,5-naphthyridinylenyl, 9-azabicyclo[3.3.1]nonanylenyl, 5-azaspiro[3.5]nonanylenyl, 2-oxa-5-azaspiro[3.5]nonanylenyl, or 2,6-diazaspiro[3.5]nonanylenyl.

[0407] In some embodiments. Ring J is as depicted in the compounds described herein.

[0408] As described above and defined herein, Ring K is phenyl, naphthyl, a 9-10 membered saturated or partially unsaturated bicyclic heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-13 membered monocyclic, bicyclic, or tricyclic heteroarylenyl with 1- 5 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0409] In some embodiments. Ring K is phenyl. In some embodiments. Ring K is naphthyl. In some embodiments. Ring K is a 9-10 membered saturated or partially unsaturated bicyclic heterocyclylenyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments. Ring K is a 5-13 membered monocyclic, bicyclic, or tricyclic heteroarylenyl with 1-5 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0410] In some embodiments, Ring K is 1,2, 3 -triazo lyl, thiazolyl, pyrazolyl, phenyl, pyridyl, pyridazinyl, pyrimidinyl, indazolyl, benzo[d]isoxazolyl, benzo[d]isothiazolyl, pyrazolo[ 1,5-a]pyrimidinyl, 2,3-dihydro-lH-pyrrolo[2,3-c]pyndmyl, 6,7-dihydro-5H-184MF-363534227Attorney Docket No.: 18395-20370.40cyclopenta[b]pyridinyl, 2,3-dihydro-1H-pyrrolo[3,2-c]pyridinyl, naphthyl, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, phthalazinyl, quinazolinyl, 2,7-naphthyridinyl, or tetrazolo[1,5-a]quinoxalinyl.

[0411] In some embodiments, Ring K is as depicted in the compounds described herein.

[0412] As described above and defined herein, Rais an optionally substituted Cn6 aliphatic or

[0413] In some embodiments, Rais an optionally substituted Ci-6 aliphatic. In some| f G (R9)gembodiments,Rais

[0414] In some embodiments. Ring Rais methyl.

[0415] In some embodiments. Ring Rais as depicted in the compounds described herein.

[0416] As described above and defined herein, Rbis hydrogen, an optionally substituted Ci-6 aliphatic, phenyl, or a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or Raand Rbare optionally taken together with their intervening atoms to form an optionally substituted 9-10 membered saturated or partially unsaturated bicyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or when Y is -C(NR)-, Rbis optionally taken together with R of -C(NR)- with their intervening atoms to form a 5-7 membered partially unsaturated heterocyclyl with 0-1 heteroatoms, m addition to the 2 nitrogen atoms within the heterocyclyl, independently selected from nitrogen, oxygen, and sulfur.

[0417] In some embodiments, Rbis hydrogen. In some embodiments, Rbis hydrogen is an optionally substituted Ci-6 aliphatic. In some embodiments, Rbis hydrogen is phenyl. In some embodiments, Rbis hydrogen is a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, Raand Rbare optionally taken together with their intervening atoms to form an optionally substituted 9-10 membered saturated or partially unsaturated bicyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, when Y is -C(NR)~, Rbis optionally taken together with R of -C(NR)- with their intervening atoms to185MF-363534227Attorney Docket No.: 18395-20370.40form a 5-7 membered partially unsaturated heterocyclyl with 0-1 heteroatoms, in addition to the 2 nitrogen atoms within the heterocyclyl, independently selected from nitrogen, oxygen, and sulfur.

[0418] In some embodiment, Rbis methyl, cyclopropyl, phenyl, -CO2H, -CH2cyclopropyl, -CH2OH, -CH2OMe, or -CH2CO2H.

[0419] In some embodiments, Ring Rbis as depicted in the compounds described herein.

[0420] As described above and defined herein, Rcis -CR2CONR2, a 5-7 membered saturated or partially unsaturated carbocyclyl or heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0421] In some embodiments, Rcis -CR2CONR2 In some embodiments, Rcis a 5-7 membered saturated or partially unsaturated carbocyclyl. In some embodiments, Rcis a 5-7 membered saturated or partially unsaturated heterocyclyl with 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Rcis a 5-6 membered heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0422] In some embodiments, Rcis -CH2CONH2, -CH(Me)CONH2, -CH2CONHMe, -CH2CONHEt, - CH2CONHCH2Ph, -CH2CONHcyclopropyl, pyrrolidin-2-onyl, piperidin-2-onyl, or isoxazolyl.

[0423] In some embodiments, Ring Rcis as depicted in the compounds described herein.

[0424] As described above and defined herein, Rdis hydrogen, or when Rcis - CR2CONR2, Rdis optionally taken together with a single R of -CR2CONR2 with their intervening atoms to form a 5-7 membered saturated or partially unsaturated heterocyclyl with 0-3 heteroatoms, in addition to the nitrogen atom to which Rdis attached, independently selected from nitrogen, oxygen, and sulfur.

[0425] In some embodiments, Rdis hydrogen.

[0426] In some embodiments. Ring Rdis as depicted in the compounds described herein.

[0427] As described above and defined herein, Re, Rr, R8, Rh, R1, R, and Rkare each independently selected from hydrogen, oxo, RA, halogen, -CN, -NO2, -OR, -SR, -NR2, - SiR3,186MF-363534227Attorney Docket No.: 18395-20370.40-S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, - OP(O)R2, -OP(O)(OR)2, -OP(O)(OR)NR2, -OP(O)(NR2)2, -NRC(O)OR, - NRC(O)R, -NRC(O)N(R)2, - NRS(O)2R, -NP(O)R2, -NRP(O)(OR)2, -NRP(O)(OR)NR2, - NRP(O)(NR2)2, -P(O)R2, -P(O)(OR)2, - P(O)(OR)NR2, and -P(O)(NR2)2, or an R group on Ring I and an R group or Ring J are optionally taken together with their intervening atoms to form a 5-8 membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0428] In some embodiments, one or more of Re, Rr, Rg, Rh, R1, RJ, and Rkis hydrogen. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis oxo. In some embodiments, one or more of Re, Rf, Rg, Rh, R1, R, and Rkis RAIn some embodiments, one or more of Re, Rr, Rg, Rh, R!, R, and Rkis halogen. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis -CN. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis -NO2. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R", and Rkis -OR. In some embodiments, one or more of Re, R, Rg, Rh, R1, R, and Rkis -SR. In some embodiments, one or more of Re, Rr, R8, Rh, R1, R, and Rkis -NR2, In some embodiments, one or more of Re, Rr, R8, Rh, R1, R, and Rkis -SiR3. In some embodiments, one or more of Re, Rr, Rg, Rh, R‘, R, and Rkis -S(O)2R. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis -S(O)2NR2. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R and Rkis -S(O)R. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R and Rkis -C(O)R In some embodiments, one or more of Re, Rr, R8, Rh, R1, R\ and Rkis -C(O)OR In some embodiments, one or more of Re, Rr, Rg, Rh, R, R', and Rkis -C(O)NR2. In some embodiments, one or more of Re, Rr, Rg, Rh, R, R, and Rkis -C(O)NROR. In some embodiments, one or more of Re, Rr, Rg, Rh, R, R, and Rkis -OC(O)R. In some embodiments, one or more of Re, Rr, R8, Rh, R, R, and Rkis -OC(O)NR2. In some embodiments, one or more of Re, Rr, R8, Rh, R1, R, and Rkis -OP(O)R2. In some embodiments, one or more of Re, Rr, R8, Rh, R1, R, and Rkis -OP(O)(OR)2. In some embodiments, one or more of Re, Rr, Rg, Rh, R’, R*, and Rkis -OP(O)(OR)NR2. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis -OP(O)(NR2)2. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis -NRC(O)OR. In some embodiments, one or more of Re, Rf, Rg, Rh, R1, R, and Rkis -NRC(O)R. In some embodiments, one or more of Re, Rr, Rg, Rh, R, R', and Rkis -NRC(O)N(R)2. In some embodiments, one or more of Re, Rr, Rg, Rh, R, R, and Rkis -NRS(O)2R. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis -NP(O)R2. In some187MF-363534227Attorney Docket No.: 18395-20370.40embodiments, one or more of Re, Rr, Rg, Rh, R1, R, and Rkis - NRP(O)(OR)2. In some embodiments, one or more of Re, Rr, Rg, Rh, R!, R\ and Rkis -NRP(O)(OR)NR2. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, R\ and Rkis -NRP(O)(NR2)2. In some embodiments, one or more of Re, Rr, Rg, Rh, R’, R", and Rkis -P(O)R2. In some embodiments, one or more of Re, Rr, Rg, Rh, R‘, Rl, and Rkis -P(O)(OR)2. In some embodiments, one or more of Rs, Rr, Rg, Rh, R1, R', and Rkis -P(O)(OR)NR2. In some embodiments, one or more of Re, Rr, Rg, Rh, R1, RJ, and Rkis -P(O)(NR2)2. In some embodiments, an R1group on Ring I and an Ri group or Ring J are taken together with their intervening atoms to form a 5-8 membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0429] In some embodiments, Reis hydrogen, oxo, fluoro, chloro, -CN, methyl, -CO2H, - CO2Me, - CONH2, -C(O)CHCH2, -OH, -OMe, -CH2CHF2, -CH2OMe, -CH2CO2H, - CH2SO2Me, -CH2CH2OH, - CH2CH2SO2Me, -CH2CH2OMe, -NHC(O)CHCH2, tetrazolyl, or N-methyltetrazolyl.

[0430] In some embodiments, Rfis hydrogen, oxo, methyl, isopropyl, -CH2cyclopropyl, - CH2cyclopentyl, -CH2cyclohexyl, -CH2morpholinyl, -CH2Ph, -CH2thiazolyl, -CH2pyrimidinyl, - CH2CH2OMe, -CH2CH2Ph, -C(O)Me, -C(O)CHCH2, -C(O)Ph, - C(O)pyrimidinyl, -NH2, -NHC(O)CHCH2, -CH2NHC(O)CHCH2, -C(O)NHC(O)CHCH2, - NHcyclohexyL -NHphenyl, or -NHpyrimidinyl,

[0431] In some embodiments, Rhis hydrogen, oxo, fluoro, methyl, ethyl, n-propyl, n-butyl, - CH2CH2OMe, -C(O)CHCH2, -NHC(O)CHCH2, -N(Me)C(O)CHCH2, -CH2NHC(O)CHCH2, or O O

[0432] In some embodiments, Rgis hydrogen, oxo, fluoro, chloro, -CN, methyl, -CONH2, -OH, or - OMe.

[0433] In some embodiments, R1is hydrogen, oxo, fluoro, chloro, methyl, -CF3, -CH2OH, -CN, -OH, -OMe, -NH2, or -N(Me)CH2CH2CH2N(Me)C(O)CHCH2.

[0434] In some embodiments, R is hydrogen, oxo, fluoro, methyl, -CH2F, -CH2OH, - CO2H, - C(O)NH2, -OH, -OMe, or -S(O)2NH2.188MF-363534227Attorney Docket No.: 18395-20370.40

[0435] In some embodiments, R1and R', are taken together by -CH2CH2- or -CH2CH2CH2-.

[0436] In some embodiments, Rkis hydrogen, oxo, fluoro, chloro, -CN, methyl, isobutyl, -CF3, - CH2CF3, -CH2OH, -CH2CO2Me, -CH(OH)Me, -CH(NH2)cyclopropyl, -CH2Ph, -OH, -OMe, -OCF3, -OiPr, OPh, -NHC(O)Me, -NHC(O)CHCH2, -S(O)2NH2, 1,2,3-triazolyl, piperdinyl, N-methylpiperdmyl, phenyl, or pyridyl.

[0437] In some embodiments, Re, Rr, Rg, Rh, R1, R, and Rkare as depicted in the compounds described herein.

[0438] As described above and defined herein, each RAis independently an optionally substituted group selected from C1-6 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.

[0439] In some embodiments, RAis an optionally substituted C1-6 aliphatic. In some embodiments, RAis an optionally substituted phenyl. In some embodiments, RAis an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic. In some embodiments, RAis an optionally substituted saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, RAis an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0440] In some embodiments, RAis C1-6 alkyl (e.g., methyl, ethyl, isopropyl). In some embodiments, RAis Ci-6 haloalkyl (e.g., -CF3, -CHF2).

[0441] In some embodiment, RAis as depicted in the compounds described herein.

[0442] As described above and defined herein, each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 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, or two R groups on the same atom are optionally taken together with their intervening atoms to form an189MF-363534227Attorney Docket No.: 18395-20370.40optionally substituted 3-7 membered saturated or partially unsaturated ring having 0-3 heteroatoms, in addition to the atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur.

[0443] In some embodiments, R is hydrogen. In some embodiments, R is an optionally substituted C1-6aliphatic. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is an optionally substituted 4-7 membered saturated or partially unsaturated carbocyclic. In some embodiments, R 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, 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 atom are optionally taken together with their intervening atoms to form optionally substituted 3-7 membered saturated or partially unsaturated ring having 0-3 heteroatoms, m addition to the atom to which they are attached, independently selected from nitrogen, oxygen, and sulfur.

[0444] In some embodiment, R is as depicted in the compounds described herein.

[0445] As described above and defined herein, each of X1and X2is independently a covalent bond, spiro-fusion between the two rings that X1or X2connect, -CR2-, -CR(OR)-, -CRF-, -CF2-, -NR-, -O-, -S-, or -S(O)2-.

[0446] In some embodiments, X1and / or X2is a covalent bond. In some embodiments, X1and / or X2is -CR2-. In some embodiments, X1and / or X2is -CR(OR)-. In some embodiments, X1and / or X2is - CRF-. In some embodiments, X1and / or X2is -CF2- In some embodiments, X1and / or X2is -NR-. In some embodiments, X1and / or X2is -O-. In some embodiments, X1and / or X is -S-. In some embodiments, X1and / or X2is -S(O)2-. In some embodiments, X1and / or X2represents spiro-fusion between the two rings that X1orX2connect.

[0447] In some embodiments, X1is a covalent bond, -NH-, or -NMe-.

[0448] In some embodiments, X2is a covalent bond, -CH2-, -CMe(OMe)-, -CMe(F)-, - CMe(CF3)-, cyclopropylenyl, difluorocyclopropylenyl, -NH-, -NMe-, -N(COMe)-, -N(CF3)-, -NEt-, -N(nPr)-, -N(nBu)-, -N(Ph)-, -N(3 -pyridyl)-, -N(4-pyridyl)-, -N(SO2Me)-, - N(CH2CHF2)-, -N(CH2cyclopropyl)-, -N(CH2Ph)-, -N(CH2CONH2)-, -N(CH2SO2Me)-, -190MF-363534227Attorney Docket No.: 18395-20370.40N(CH2CH2CHF2)-, -N(CH2CH2Ph)-, -N(CH2CH2CO2H)-, - N(CH2CH2CONH2)-, -N(CH2CH2CN)-, -N(CH2CH2OMe)-, -N(CH2CH2SO2Me)-, -0-, -S-, or -S(O)2-.

[0449] In some embodiments, X2represents spiro-fusion between the two rings thatconnects, e.g.,

[0450] In some embodiments, X1and X2are as depicted in the compounds described herein.

[0451] As described above and defined herein, Y1is a C1-3 hydrocarbon chain wherein each methylene is optionally substituted with -CR2-, -CR(OR)-, -C(O)-, -C(NR)-, -C(NOR)-, -S(O)-, or -S(O)2-.

[0452] In some embodiments, Y1is a C1-3 hydrocarbon chain wherein each methylene is optionally substituted with -CR2-, -CR(OR)-, -C(O)-, -C(NR)-, -C(NOR)-, -S(O)-, or -S(O)2-.

[0453] In some embodiments, Y1is a C1-3 hydrocarbon chain. In some embodiments, Y1is -CR2-. In some embodiments, Y!is -CR(OR)- In some embodiments, Y1is -C(O)-. In some embodiments, Y1is - C(NR)-. In some embodiments, Y1is -C(NOR)-. In some embodiments, Y1is -S(O)-. In some embodiments, Y1is -S(O)2-.

[0454] In some embodiments, Y1is -CH2-, -CH2C(O)-, -NHCH2C(O)-, -CH2CH2C(O)-, - CH2CH(OH)C(O)-, -C(O)-, -C(NH)-, -C(NOH)-, -S(O)-, or -S(O)2-.

[0455] In some embodiment, Y1is as depicted in the compounds described herein.

[0456] As described above and defined herein, s is 0 or 1.

[0457] In some embodiments, s is 0. In some embodiments, s is 1.

[0458] In some embodiment, s is as depicted in the compounds described herein.

[0459] As described above and defined herein, each of e, f, g, h, 1, j, and k are independently 0, 1, 2, 3, or 4.

[0460] In some embodiments, e is 0. In some embodiments, e is 1. In some embodiments, e is 2. In some embodiments, e is 3, In some embodiments, e is 4.191MF-363534227Attorney Docket No.: 18395-20370.40

[0461] In some embodiments, f is 0. In some embodiments, f is 1. In some embodiments, f is 2. In some embodiments, f is 3. In some embodiments, f is 4.

[0462] In some embodiments, g is 0. In some embodiments, g is 1. In some embodiments, g is 2. In some embodiments, g is 3. In some embodiments, g is 4.

[0463] In some embodiments, h is 0. In some embodiments, h is 1. In some embodiments, h is 2. In some embodiments, h is 3. In some embodiments, h is 4.

[0464] In some embodiments, i is 0. In some embodiments, i is 1, In some embodiments, i is 2. In some embodiments, i is 3. In some embodiments, i is 4.

[0465] In some embodiments, j is 0. In some embodiments, j is 1. In some embodiments, j is 2. In some embodiments,] is 3. In some embodiments,] is 4.

[0466] In some embodiments, k is 0. In some embodiments, k is 1. In some embodiments, k is 2. In some embodiments, k is 3. In some embodiments, k is 4.

[0467] In some embodiment, e, f, g, h, i, j, and k are as depicted in the compounds described herein.

[0468] In some embodiments, the DCAF1 binding moiety of formula I-dddd is192MF-363534227Attorney Docket No.: 18395-20370.40

[0469] In some embodiments, the DCAF1 binding moiety of formula I-eeee is

[0470] In certain embodiments, the present invention provides a compound of I-dddd represented by any one of the following formulae:193MF-363534227Attorney Docket No.: 18395-20370.40S-tMdd-7 I-dddd-8l-dtkld-H3-dddd-13 Mddd-I4194MF-363534227Attorney Docket No.: 18395-20370.40I-dddd45or a pharmaceutically acceptable salt thereof.

[0471] In certain embodiments, the present invention provides a compound of formula I-eeee represented by any one of the following formulae:195MF-363534227Attorney Docket No.: 18395-20370.40I-eeee-33or a pharmaceutically acceptable salt thereof.196MF-363534227Attorney Docket No.: 18395-20370.40

[0472] As defined above and described herein, said compound of formula I-dddd or I-WG. ( WG ]eeee is optionally substituted withk- ■'. wherein - - is a warhead group attached to a modifiable carbon, oxygen, nitrogen or sulfur atom in formula I-dddd or I-eeee or a substitution or replacement of any defined group in formula I-dddd or I-eeee (e.g., substitution or replacement of Re, Rr, R8, Rh, R1, R, or Rk).

[0473] In some embodiments, the warhead group is -L2-Y, wherein:L2is a covalent bond or a bivalent Ci-s saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one, two, or three methylene units of L2are 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, Ci-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 Regroups; and each Reis independently selected from -Q-Z, oxo, NO2, halogen, CN, a suitable leaving group, or a Cl- 6 aliphatic optionally substituted with oxo, halogen, NO2, or CN, wherein: Q is a covalent bond or a bivalent C1-6 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 —SO?—, — N(R)C(O)—, — C(O)N(R)—, — N(R)SO?—, or — SO2N(R)-; and Z is hydrogen or C1-6 aliphatic optionally substituted with oxo, halogen, NO2, or CN.

[0474] In certain embodiments, L2is a covalent bond.

[0475] In certain embodiments, L2is a bivalent Cl -8 saturated or unsaturated, straight or branched, hydrocarbon chain. In certain embodiments, L2is — CH? —.

[0476] In certain embodiments, L2is a covalent bond, — CH —...

Claims

1. Attorney Docket No.: 18395-20370.402.CLAIMS3.What is claimed is:

5.

6. pharmaceutically acceptable salt thereof, wherein SBM is a compound of Formula (I),8. 10.or a pharmaceutically acceptable salt thereof, wherein:11.R101aand R101bare each independently H or halogen,12.R102is H, (Ci-C6)alkyl, or (Cs-Cr cycloalkyl,13.R103is (Ci-Cejalkyl, halo(Ci-Ce)alkyl, (C3-C6)cycloalkyl, 3- to 7 -membered heterocyclyl, -(Ci-C6)alkylene-(C3-C6)cycloalkyl, or -(Ci-C6)alkylene-(3- to 7- membered heterocyclyl), wherein (Ci-Cejalkyl, (C3-C6)cycloalkyl, (C3- C6)cycloalkyl of -(Ci-C6)alkylene-(C3-C6)cycloalkyl, or (3- to 7-membered heterocyclyl) of -(Cj-C6)alkylene-(3- to 7-membered heterocyclyl) is each substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of (Ci-Ce)alkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Ci- C6)alkyl, and halo(Ci-C6)alkoxy,14.or R10and R103together with the nitrogen atom to which they are attached form 5- to 7-membered heterocyclyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of (Ci-Celalkyl, (Ci-C6)alkoxy, cyano, halogen, halo(Cj-C6)alkyl, and halo(Ci-C6)alkoxy;15.R104is H, (C6-Cio)aryl, or 5- to 10-membered heteroaryl, wherein (Ce-Cio)aryl or 5- to 10-membered heteroaryl is each substituted with 0, 1, 2, or 3 substituents each16.35317.MF-363534227 Attorney Docket No.: 18395-20370.4018.independently selected from the group consisting of halogen, cyano, (Ci-C6)alkyl, (Ci-C6)alkoxy, halo(Ci-C6)alkyl, halo(Cj-C6)alkoxy, and -NR104aR104b, wherein:19.each R104aand R104bis independently H or (C]-C6)alkyl;20.R105is H, cyano, or (Ci-Ce)alkoxy; and21.Rpis phosphonic acid, phosphonate, phosphonamidate, or phosphondiamidate;22.L is a bivalent moiety'; and23.DIM is a degradation inducing moiety,24.wherein25.

26. is attached to a modifiable carbon, oxygen, or nitrogen atom.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ri01ais F.

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R101bis H4. The compound of claim I, or a pharmaceutically acceptable salt thereof, wherein R101ais F and Ri01bis H.

5. The compound of claim 1, or a pharmaceutically acceptable salt thereof’ wherein R101aand R101bare each F.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R102is methyl or ethyl.

7. The compound of any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein R103is (Ci-C6)alkyl, halo(Ci-C6)alkyl, (C3-C6)cycloalkyl, 3- to 7- membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl).

8. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R103is halo(Ci-C6) alkyl.

9. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R103is (C -Csjcycloalkyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, halo(Ci-C6)alkyl, and halo(Ci- C6)alkoxy.

10. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R103is 3 -to 7-membered heterocyclyl.36.35437.MF-363534227 Attorney Docket No.: 18395-20370.4011. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R103is -(Ci-C6)alkylene-[3-to 7-membered heterocyclyl substituted with 0 or 1 (Ci- C6)alkyl].

12. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R103is (Ci-Cejalkyl substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halo, (Ci-C6)alkoxy, and halo(Ci-C6)alkoxy.

13. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R10341.

42.

14. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein43.R1“ R 10344.of Formula (I) is46. 48.35549.MF-363534227 Attorney Docket No.: 18395-20370.4051.

52.

15. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R1 2and R103together with the nitrogen atom to which they are attached form 6-membered heterocyclyl.

16. The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein55.

56. of Formula (I) is.

17. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof wherein R104is H.

18. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein R104is (Ce-Ciolaryl or 5- to 10-membered heteroaryl.

19. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein R104is phenyl substituted with 0, 1, 2, or 3 halogen.

20. The compound of claim 19, or a pharmaceutically acceptable salt thereof, wherein61.R62. 63.104IS ^^ / .

21. The compound of claim 19, or a pharmaceutically acceptable salt thereof, wherein65.F67.

22. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein R104is pyridinyl substituted with 0 or 1 -NR104aR104b.

23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein72. 74.35675.MF-363534227 Attorney Docket No.: 18395-20370.4024. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein78.

25. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein R105is H.

26. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein R103is cyano.

27. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein Rl°3is methoxy.

28. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt84.thereof, wherein Rpis85.

86. , wherein RP1and RP2are each independently -OH, - N"' ]. N' ] ORPa, N-linked amino acid, N-linked amino acid ester, or87.

88. , wherein89.

90. is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and -C(O)ORPE, wherein:91.eachRPais independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, (C6-Cio)aryl, or (C3- Cr cycloalkyl, wherein (Cj -C6)alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-C6)alkoxy; and92.eachRPEis independently (Ci-QGalkyl, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci- Cr alkoxy, (C3-C6)cycloalkyl, (C5-C3)spirocycloal kyl, -(Ci-C6)alkylene-(C6- C;0)aryl, -((. T-Ce^alkylene-lCi-Cslalkoxy, -(Ci-C6)alkylene-(C3-(27)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, or (C3- C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

29. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt94.VW / 96. 98.I _99.thereof, wherein Rpis100.

101. ", wherein RP1and RP2are each independently -OH, - 1 O102.

103. RPa, -NRPaalCRPaa2RPaa3C(O)OH, -NRPaalCRPaa2RPaa3C(O)ORPaa4, or 357104.MF-363534227 Attorney Docket No.: 18395-20370.40105.wherein H i.s substi.tuted wi.th 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and -C(O)ORPE, wherein: each RPais independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, (C6-Cio)aryl, or (C3- Cr cycloalkyl, wherein (Ci-Ce alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-C6)alkoxy; eachRPEis independently (Ci-C6)alkyl, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci- C6)alkoxy, (C3-C6)cycloalkyl, (Ch-C8)spirocycloalkyl, -(Ci-C6)alkylene-(C6- Cio)aryl, -(Ct-C6)alkylene-(Ci-C6)alkoxy, -(Cl-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C^alkyl, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, or (C3- C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen,106.each RPaalis independently H or (Ci-CeOalkyl;107.each RPaa2is independently H or (Ci-Ccjalkyl, and each RPaa3is independently H, (Cj- C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; and108.each RPaa4is independently (Ci-C6)alkyl, halolC-Cslalkyl, -(Cl-(36)alkylene-(Ci- C6)alkoxy, (C3-C6)cy cloal ky 1, (C5-C8)spirocy cloalky 1, -(C 1 -C6)alky 1 ene-(C6- Cio)aryl, -(C1-C6)alkylene-(Ci-C6)alkoxy, -(C -C6)alkylene-(C3-C7)cy cloalky 1, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (C3-C6)cycloalkyl, (C5-C8)spirocycloalkyl, or (C3- Cvlcycloalkyl of -(Cl-(36)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

30. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt110.Rp1-P=O111.i112.thereof, wherein RpisrP2, wherein RP1and RP2are each -OH.

31. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt115.

116. Rp1-P=O117.i118.thereof, wherein RpisrP2, wherein RP1is -OH and RP2is N-linked amino acid.119.358120.MF-363534227 Attorney Docket No.: 18395-20370.4032. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt » / WV122.Rp1-P=O123.thereof wherein RpisrP2, wherein RP1is -ORPaand RP2is N-linked amino acid ester, wherein RPais (Ci-C6)alkyl, halo(Ci -Chalky 1, (C6-Cio)aryl, or (C3- C6)cycloalkyl, wherein (Ci-Ce alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (Ci-Cc alkoxy.

33. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt125.Rp1-P=O126.I127.thereof, wherein RpisrP2, wherein RP1and RP2are each independently N-lmked amino acid.

34. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt •A / W129.Rp1-P=O130.I131.thereof, wherein RpisrP2, wherein RPiand RP2are each independently N-linked amino acid ester.

35. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt133.Rp1-P-0134.thereof, wherein RpisrF>2, wherein RPiis N-linked amino acid and RP2is j;—N J ^_NJ135.whereiniSsubstituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and -COOH.

36. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt JVW137.Rp1-P=O138.thereof wherein RpisrF>2, wherein RP1is N-lmked amino acid ester and RP2is N J. N J.

140.

141. , wherein jssubstituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and ester.

37. The compound of claim 32, or a pharmaceutically acceptable salt thereof, wherein RPais phenyl.

38. The compound of claim 32, or a pharmaceutically acceptable salt thereof, wherein RPais ethyl.

39. The compound of claim 32, or a pharmaceutically acceptable salt thereof, wherein RPais -CH2CF3.145.359146.MF-363534227 Attorney Docket No.: 18395-20370.4040. The compound of claim 32, or a pharmaceutically acceptable salt thereof, wherein RPa149.

150. , cyclopropyl, cyclopentyl. or cyclohexyl.

41. The compound of claim 35, or a pharmaceutically acceptable salt thereof, wherein RP2153.

42. The compound of claim 36, or a pharmaceutically acceptable salt thereof, wherein RP2156.is157.

158. N J, wherein l159.

160. i—N T-- J i.ssubstituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, and -C(O)ORPE, wherein each RPEis independently (Ci-C6)alkyl, halofCi-Cejalkyl, -(Ci-C6)alkylene- (Ci-C6)alkoxy, (Cs-Celcycloalkyl, (C5-Cs)spirocycloalkyl, -(Ci-C6)alkylene-(C6- Cio)aryl, -(Ci -Chalky lene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Ci-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-C6)alkyl, (Cs-Cc cycloalkyl, (Cs-Csjspirocycloalkyl, or (C3-C?)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

43. The compound of claim 42, or a pharmaceutically acceptable salt thereof, wherein163.

164.

44. The compound of claim 43, or a pharmaceutically acceptable salt thereof, wherein each R165. 166.PEIS.167.360168.MF-363534227 Attorney Docket No.: 18395-20370.4045. The compound of claim 36, or a pharmaceutically acceptable salt thereof, wherein RP2171.

172. or 46. The compound of any one of claims 31, 33, 35, and 41, or a pharmaceutically acceptable salt thereof, wherein each N-lmked amino acid is independently N-lmked a- ammo acid.

47. The compound of claim 46, or a pharmaceutically acceptable salt thereof, wherein each N-linked amino acid is independently -NRPaalCRPaa2RPaa3C(O)OH, wherein: each RPaalis independently H or (Ci-Csjalkyl; and174.each RPaa2is independently H or (Ci-C6)alkyl, and each RPaa3is independently H, (Ci- C6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(Ci-C6)alkylene-(C6-Cio)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (Cz3-Ce)cy cloalky I.

48. The compound of any one of claims 32, 34, 36, 37 to 40, and 42 to 45, or a pharmaceutically acceptable salt thereof, wherein each N-lmked amino acid ester is independently N-lmked a-amino acid ester.

49. The compound of claim 48, or a pharmaceutically acceptable salt thereof, wherein each N-linked amino acid ester is independently -NRPaaiCRPaa2RPaa3C(O)ORPaa4, wherein:177.each RPaalis independently H or (Ci-C6)alkyl;178.each RPaa2is independently H or (Ci-C6)alkyl, and each RPaa3is independently H, (Ci- Cz6)alkyl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, or -(C1-C6)alkylene-(C6-C10)aryl; or RPaa2and RPaa3, together with the carbon atom to which they are attached form (C3-C6)cycloalkyl; and179.eachRPaa4is independently (Ci-Ce)alkyl, halo(Ci-C6)alkyl, -(Ci-C6)alkylene-(Ci- C6)alkoxy, (Cs-Cc cycloalkyl, (Cs-Csjspirocycloalkyl, -(Ci-C6)alkylene-(C6- Cto)aryl, -(Ci-C6)alkylene-(Ci-C6)alkoxy, -(Ci-C6)alkylene-(C3-C7)cycloalkyl, 3- to 7-membered heterocyclyl, or -(Cj-C6)alkylene-(3- to 7-membered heterocyclyl), wherein (Ci-Ce)alkyl, (C3-C6)cycloalkyl, (Cz5-Cs)spirocycloalkyl, or (C3-C7)cycloalkyl of -(Ci-C6)alkylene-(C3-C7)cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.180.361181.MF-363534227 Attorney Docket No.: 18395-20370.4050. The compound of claim 49, or a pharmaceutically acceptable salt thereof, wherein184.

185.

51. The compound of claim 50, or a pharmaceutically acceptable salt thereof, wherein187.

52. The compound of claim 50, or a pharmaceutically acceptable salt thereof, wherein190.

191. RPaa4is53. The compound of Claim 50, or a pharmaceutically acceptable salt thereof, wherein194.

195.

54. The compound of any one of claims 47 and 49 to 53, or a pharmaceutically acceptable salt thereof, wherein RPaalis H.

55. The compound of any one of claims 47 and 49 to 53, or a pharmaceutically acceptable salt thereof, wherein RPaalis methyl.

56. The compound of any one of claims 47 and 49 to 55, or a pharmaceutically acceptable salt thereof, wherein RPaa2is H,198.362199.MF-363534227 Attorney Docket No.: 18395-20370.4057. The compound of any one of claims 47 and 49 to 55, or a pharmaceutically acceptable salt thereof, wherein RPaa2is methyl,58. The compound of any one of claims 47 and 49 to 57, or a pharmaceutically acceptable salt thereof, wherein RPaa3is methyl.

59. The compound of any one of claims 47 and 49 to 57, or a pharmaceutically acceptable203.salt thereof, wherein RPaa3is ethvl,204.

205. , or -CH2OCH3.

60. The compound of any one of claims 47 and 49 to 57, or a pharmaceutically acceptable207.salt thereof, wherein R208. 209.Paa3is61. The compound of any one of claims 47 and 49 to 53, or a pharmaceutically acceptable salt thereof, wherein RPaa2and RPaa3, together with the carbon atom to which they are attached form cyclopropyl.

62. The compound of any one of claims 1-61, or a pharmaceutically acceptable salt thereof, wherein the 4-azaspiro[2.4]heptane ring of Formula (I) covalently attached to R104and R105is substituted by -NHC(0)RlocDIM, -OR10CDIM, phenyl, (C3- C6)cycloalkyl, 5- to 6-membered heteroaryl, or 4- to 6-membered heterocyclyl, wherein each of said phenyl, (C3-C6)cycloalkyl, 5- to 6-membered heteroaryl, and 4- to 6-membered heterocyclyl is substituted with -OR10CDIM, -NHRIOCDIM, -[N(Ci- C4)alkyl]RlocDIM, or -R,0CDIM, wherein said 4- to 6-membered heterocyclyl is optionally substituted further with oxo, and wherein RluCis a chemical spacer unit.

63. The compound of claim 62, or a pharmaceutically acceptable salt thereof, wherein R1 Cis (Ci-Cio)alkylene or (C2-Cio)alkynelene, each of which is optionally substituted with one or more groups selected from the group consisting of halo and oxo, and wherein said (Ci-Cio)alkylene and (C2-Cio)alkynelene may also be optionally interrupted by one or more heteroatoms selected from the group consisting of S, N, and O, and / or optionally interrupted by one or more rings selected from the group consisting of 5- to 7-membered heteroaryl, (C -C6)cycloakyl, phenyl, and 4- to 7- membered heterocyclyl.

64. The compound of claim 62, or a pharmaceutically acceptable salt thereof, wherein R10Cis (Ci-Cio)alkylene, (C2-Cio)alkynelene, -(CH2)mC(O)NH[(CH2)O]v(CH2)!1, - (CH2)O[(CH2)O]v(CH2)n, -(C2-C8)alkynelene[4- to 7-membered heterocyclyl], 4- to 7- membered heterocyclyl, [(CH2)O]v(CH2)n, or -(CFl2)nC(O)NH[4- to 7-membered heterocyclyl], wherein m, n, and v are each independently 0, 1, 2, 3, 4, 5, or 6.213.363214.MF-363534227 Attorney Docket No.: 18395-20370.4065. The compound of claim 62, or a pharmaceutically acceptable salt thereof, wherein217.

218. indicates the position to which DIM is attached.

66. The compound of any one of preceding claims, or a pharmaceutically acceptable salt thereof, wherein DIM is a CRBN, VHL, LAP, or MDM2 based E3 binder.

67. The compound of any one of preceding claims, or a pharmaceutically acceptable salt O O222. 224.364225.MF-363534227 Attorney Docket No.: 18395-20370.40227. 229.YDIMIS O or CH2,230.DDIMis O, NH, or a bond; and231.U is absent or C(0).

68. The compound of any one of claims 1 to 67, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (B-Rla), (B-Rlb), (B-RP),233.R103 N R102234.R105 X,0R"f t \ / J oR104235.L236.(B-R2), (B-R3), (B-R4), (B-R5), or (B-RXa):RP' R101b238. 240.365241.MF-363534227 Attorney Docket No.: 18395-20370.40243. 245.366246.MF-363534227 Attorney Docket No.: 18395-20370.40248.

69. The compound of any one of claims 1-67, or a pharmaceutically acceptable salt251.thereof, wherein252.

253. is attached to a modifiable carbon, nitrogen, or oxygen atom of Rp.

70. The compound of any one of claims 1-14 and 17-67, or a pharmaceutically acceptable255.salt thereof, wherein256.

257. is attached to a modifiable carbon, nitrogen. or oxygen atom of R10271. The compound of any one of claims 1-14 and 17-67, or a pharmaceutically acceptable259.salt thereof, wherein260.

261. is attached to a modifiable carbon, nitrogen, or oxygen atom of R1(.

72. The compound of any one of claims 1-5 and 15-67, or a pharmaceutically acceptable salt thereof, wherein R102and R103together with the nitrogen atom to which they are attached form 5- to 7-membered heterocyclyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of (Ci-C6)alkyl, (Cj-C6)alkoxy,263.367264.MF-363534227 Attorney Docket No.: 18395-20370.40265.cyano, halogen, halo Ci-Cs alkyl, and halo(Ci-C6)alkoxy, and266.

267. attached to a modifiable carbon, nitrogen, or oxygen atom of the 5- to 7-membered heterocyclyl or a substituent thereof.

73. The compound of any one of claims 1-16 and 18-67, or a pharmaceutically acceptable269.I DIM J270.salt thereof, wherein271.

272. is attached to a modifiable carbon, nitrogen. or oxygen atom of R10474. The compound of any one of claims 1-24 and 27-67, or a pharmaceutically acceptable274.salt thereof, wherein275.

276. is attached to a modifiable carbon, nitrogen. or oxygen atom of R10575. The compound of any one of claims 1-67, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (B-VI):278.or a pharmaceutica279.

280. lly acceptable salt thereof, wherein one Rxis and each remaining Rxis H.

76. The compound of any one of the preceding claims, or a pharmaceutical ly acceptable salt thereof, wherein the compound of Formula (I) is a compound of Formula (I-A-l), (I-A-2), (I-A-3), (I-A-4), (I-A-5), (I-A-6), (I-B- 1), (I-B-2), (I-B-3), (I-B-4), (I-B-5), (I- B-6), (I-C-l), (I-C-2), (I-C-3), (I-C-4), (l-C-5), (I-C-6), (I-D-l), (I-D-2), (I-D-3), (I-D- 4), (I-D-5), (I-D-6), (I-E-1), (I-E-2), (I-E-3), (I-E-4), (l-E-5), (I-E-6), (I-F-l), (I-F-2),282.368283.MF-363534227 Attorney Docket No.: 18395-20370.40284.(LF-3), (I-F-4), (I-F-5), (I-F-6), (I-G-l), (I-G-2), (I-G-3), (I-G-4), (I-G-5), (I-G-6), (I- H-l), (I-H-2), (I-H-3), (I-H-4), (I-H-5), or (I-H-6).

77. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is selected from the group consisting of the compounds of Table 1 A, Table IB, and Table 1C.

78. The compound of any one of claims 1-77, wherein DIM is an E3 ubiquitin ligase binding moiety (LBM) selected from the group consisting of a cereblon E3 ubiquitin ligase binding moiety, a VHL E3 ubiquitin ligase binding moiety, an IAP E3 ubiquitin ligase binding moiety, and an MDM2 E3 ubiquitin ligase binding moiety.

79. The compound of any claim 78, wherein the E3 ubiquitin ligase binding moiety (LBM) is a cereblon E3 ubiquitin ligase binding moiety.

80. The compound of claim 78, wherein the E3 ubiquitin ligase binding moiety (LBM) is a VHL E3 ubiquitin ligase binding moiety.

81. The compound of claim 78, wherein the E3 ubiquitin ligase binding moiety (LBM) is a IAP E3 ubiquitin ligase binding moiety.

82. The compound of claim 78, wherein the E3 ubiquitin ligase binding moiety (LBM) is an MDM2 E3 ubiquitin ligase binding moiety.

83. A pharmaceutical composition comprising the compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.

84. A medicament comprising a compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 83.

85. A method of treating a disease or condition responsive to the modulation (e.g., inhibition) of STAT6 in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of the compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 83.

86. A compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 83, for use as a drug.

87. A compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 83, for use in the treatment of a disease or condition responsive to modulation (e.g., inhibition) of STAT6 m a subject.296.369297.MF-363534227 Attorney Docket No.: 18395-20370.4088. Use of a compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 83, for use in the preparation of a medicament.

89. The use of claim 88, wherein the medicament is intended for the treatment of a disease or condition responsive to the modulation (e.g., inhibition) of STAT6 in a subject.

90. The method of claim 85, the compound for use of claim 87, or the use of claim 89, wherein the disease or condition is selected from the group consisting of an inflammatory disorder, autoimmune disorder, an allergic disorder, and a skin disorder.

91. The method of claim 85, the compound for use of claim 87, or the use of claim 89, wherein the disease or condition is selected from the group consisting of atopic dermatitis, prurigo nodularis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and chronic obstructive pulmonary disease.302.370303.MF-363534227

Images