3-(5-HYDROXY-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF

Description

FIELD OF THE DISCLOSURE

The present disclosure relates to 3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione compounds and compositions and their use for the treatment of IKAROS Family Zinc Finger 2 (IKZF2)-dependent diseases or disorders or where reduction of IKZF2 or IKZF4 protein levels can ameliorate a disease or disorder.

BACKGROUND OF THE DISCLOSURE

IKAROS Family Zinc Finger 2 (IKZF2) (also known as Helios) is one of the five members of the Ikaros family of transcription factors found in mammals. IKZF2 contains four zinc finger domains near the N-terminus which are involved in DNA binding and two zinc finger domains at the C-terminus which are involved in protein dimerization. IKZF2 is about 50% identical with Ikaros family members, Ikaros (IKZF1), Aiolos (IKZF3), and Eos (IKZF4) with highest homology in the zinc finger regions (80%+identity). These four Ikaros family transcription factors bind to the same DNA consensus site and can heterodimerize with each other when co-expressed in cells. The fifth Ikaros family protein, Pegasus (IKZF5), is only 25% identical to IKZF2, binds a different DNA site than other Ikaros family members and does not readily heterodimerize with the other Ikaros family proteins. IKZF2, IKZF1 and IKZF3 are expressed mainly in hematopoietic cells while IKZF4 and IKZF5 are expressed in a wide variety of tissues. (John, L. B., et al., (2011), Mol. Immunol. 48:1272-1278; Perdomo, J., et al., (2000), J. Biol. Chem. 275:38347-38354.)

IKZF2 is believed to have an important role in the function and stability of regulatory T cells (Tregs). IKZF2 is highly expressed at the mRNA and protein level by regulatory T-cell populations. Knockdown of IKZF2 by siRNA has been shown to result in downregulation of FoxP3 and to impair the ability of isolated human CD4+CD25+ Tregs to block T-cell activation in vitro. Moreover, overexpression of IKZF2 in isolated murine Tregs has been shown to increase expression of Treg related markers such as CD103 and GITR and the IKZF2 overexpressing cells showed increased suppression of responder T-cells. IKZF2 has also been found to bind the promoter of FoxP3, the defining transcription factor of the regulatory T-cell lineage, and to affect FoxP3 expression.

Knockout of IKZF2 within FoxP3-expressing Tregs in mice has been shown to cause activated Tregs to lose their inhibitory properties, to express T-effector cytokines, and to take on T-effector functions. IKZF2 knockout mutant mice develop autoimmune disease by 6-8 months of age, with increased numbers of activated CD4 and CD8 T cells, follicular helper T cells, and germinal center B cells. This observed effect is believed to be cell intrinsic, as Rag2−/− mice given bone marrow from IKZF2 knockout mice, but not bone marrow from IKZF2+/+ develop autoimmune disease. Direct evidence that IKZF2 affects regulatory T-cell function has been shown in the analysis of mice in which IKZF2 was deleted only in FoxP3 expressing cells (FoxP3-YFP-Cre Heliosfl/fl). The results showed that the mice also develop autoimmune disease with similar features as observed in the whole animal IKZF2 knockout. Moreover, pathway analysis of a CHIP-SEQ experiment has also suggested that IKZF2 is affecting expression of genes in the STAT5/IL-2Rα pathway in regulatory T-cells. This effect of IKZF2 loss was shown to be more apparent after an immune challenge (viral infection or injection with sheep's blood), and it was noted that after immune stimulation, the IKZF2 negative regulatory T cells began to take on features of effector T cells. (Getnet, D., et al., Mol. Immunol. (2010), 47:1595-1600; Bin Dhuban, K., et al., (2015), J. Immunol. 194:3687-96; Kim, H-J., et al., (2015), Science 350:334-339; Nakawaga, H., et al., (2016) PNAS, 113: 6248-6253)

Overexpression of Ikaros isoforms which lack the DNA binding regions have been shown to be associated with multiple human haematological malignancies. Recently, mutations in the IKZF2 gene, which lead to abnormal splicing variants, have been identified in adult T-cell leukemias and low hypodiploid acute lymphoblastic leukemia. It has been proposed that these isoforms, which are capable of dimerization, have a dominant negative effect on Ikaros family transcription factors which primes the development of lymphomas. IKZF2 knockout mutants that survive into adulthood do not develop lymphomas, supporting this hypothesis (Asanuma, S., et al., (2013), Cancer Sci. 104:1097-1106; Zhang, Z., et al., (2007), Blood 109:2190-2197; Kataoka, D., et al., (2015), Nature Genetics 47:1304-1315.)

Currently, anti-CTLA4 antibodies are used in the clinic to target Tregs in tumors. However, targeting CTLA4 often causes systemic activation of T-effector cells, resulting in excessive toxicity and limiting therapeutic utility. Up to ¾ of patients treated with a combination of anti-PD1 and anti-CTLA4 have reported grade 3 or higher adverse events (National Cancer Institute, Division of Cancer Treatment & diagnosis, Common Terminology for Adverse Events (CTCAE), https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm). Thus, a strong need exists to provide compounds that target Tregs in tumors without causing systemic activation of T-effector cells.

An IKZF2-specific degrader has the potential to focus the enhanced immune response to areas within or near tumors providing a potentially more tolerable and less toxic therapeutic agent for the treatment of cancer.

SUMMARY OF THE DISCLOSURE

The compounds of the disclosure have use as therapeutic agents, particularly for cancers and related diseases. In one aspect, the compounds of the disclosure have IKZF2 degrader activity, preferably having such activity at or below the 50 μM level, and more preferably having such activity at or below the 10 μM level. In another aspect, the compounds of the disclosure have degrader activity for IKZF2 that is selective over one or more of IKZF1, IKZF3, IKZF4, and/or IKZF5. In another aspect, the compounds of the disclosure have degrader activity for both IKZF2 and IKZF4. The compounds of the disclosure have usefulness in treating cancer and other diseases for which such degrader activity would be beneficial for the patient. For example, while not intending to be bound by any theory, the inventors believe that reducing levels of IKZF2 in Tregs in a tumor may allow the patient immune system to more effectively attack the disease. In summary, the present disclosure provides novel IKZF2 degraders useful for the treatment of cancer and other diseases.

A first aspect of the present disclosure relates to compounds of Formula (I′):

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wherein:

X₁and X₂are each independently H, (C₁-C₄)alkyl, (C₁-C₆)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₆)haloalkoxy, (C₃-C₇)cycloalkyl, halogen, —CN, —OH, or —NH₂;

R_xis H or D;

R₁is

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each R₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —CN, —OH, or —NH₂; or

two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4-to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S; or

R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂;

each R₃is (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —OH, or —NH₂;

R₄is —OR₅or —NR₆R_6′;

R₅is H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S;

R₆and R_6′ are each independently H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂; or

R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈; or

each R₇is (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₉;

each R₈is independently at each occurrence halogen, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, —CN, —OH, —NR₁₃R₁₄, —NH₂, —O(C₃-C₇)cycloalkyl, —O-4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, —O(C₆-C₁₀)aryl, or —O-5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkoxy is optionally substituted with one to three R₁₀and the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one to three R₁; or

two R₈together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅; or two R₈when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from 0, N, and S; or two R₈together with the same atom to which they are attached form a ═(O);

each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, (C₃-C₆)cycloalkyl, —OH, —CN, —NH₂, or —NR₁₃R₁₄; or

two R₉together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one or more substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂; or two R₉when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from 0, N, and S;

each R₁₀is independently at each occurrence selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S;

each R₁₁is independently at each occurrence selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, and —NH₂;

each R₁₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, or —NH₂;

two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

R₁₃and R₁₄are each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S;

two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

m and m1 are each independently 0, 1 or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≤4;

or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In one embodiment, the present disclosure relates to compounds of Formula (I′) having the structure of Formula (I):

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wherein:

R_xis H or D;

R₁is

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each R₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —CN, —OH, or —NH₂; or

two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S; or

R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂;

each R₃is (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —OH, or —NH₂;

R₄is —OR₅or —NR₆R_6′;

R₆and R_6′ are each independently H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇; or

R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈; or

each R₈is independently at each occurrence halogen, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, —CN, —OH, or —NH₂, wherein the alkoxy is optionally substituted with one to three substituents independently selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S; or

two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂; or

two R₉together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one or more substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂;

m and m1 are each independently 0, 1 or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≤4;

or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another aspect, the present disclosure relates to compounds of Formula (I′) or Formula (I′) or Formula (I), wherein:

R_xis H or D;

R₁is

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each R₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —CN, —OH, or —NH₂; or

two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S; or

each R₃is (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —OH, or —NH₂;

R₄is —OR₅or —NR₆R_6′;

each R₈is independently at each occurrence halogen, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —CN, —OH, or —NH₂; or

two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂; or

m and m1 are each independently 0, 1 or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≤4;

or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In one aspect of the disclosure, the hydrogens in the compound of Formula (I′) or Formula (I′) are present in their normal isotopic abundances. In a preferred aspect of the disclosure, the hydrogens are isotopically enriched in deuterium (D), and in a particularly preferred aspect of the invention the hydrogen at position R_xis enriched in D, as discussed in more detail concerning isotopes and isotopic enrichment below.

Another aspect of the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient. The pharmaceutical composition is useful in the treatment of IKZF2-dependent diseases or disorders. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

In another aspect, the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient for use in the treatment of an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder. The pharmaceutical composition is useful in the treatment of IKZF2-dependent diseases or disorders. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

Another aspect of the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient. The pharmaceutical composition is useful in the treatment of diseases or disorders affected by the reduction of IKZF2 protein levels. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

In another aspect, the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient for use in the treatment of a disease or disorder affected by the reduction of IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the disease or disorder. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

In another aspect, the present disclosure relates to a method of degrading IKZF2. The method comprises administering to the patient in need thereof a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

Another aspect of the present disclosure relates to a method of modulating IKZF2 protein levels. The method comprises administering to the patient in need thereof a compound of Formula (F) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

In another aspect, the present disclosure relates to a method of decreasing IKZF2 protein levels. The method comprises administering to the patient in need thereof a compound of Formula (F) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

Another aspect of the present disclosure relates to a method of reducing the proliferation of a cell. The method comprises administering to the patient in need thereof a compound of Formula (F) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof and reducing IKZF2 protein levels.

In another aspect, the present disclosure relates to a method of treating cancer. The method comprises administering to the patient in need thereof a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In one embodiment, the cancer is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In yet another embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC). In another embodiment, the cancer is a cancer for which the immune response is deficient or an immunogenic cancer.

Another aspect of the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient for use in the treatment of an IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient in the manufacture of a medicament for treating of an IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a method for treating an IKZF2-dependent disease or disorder comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

In another aspect, the present disclosure relates to a method for treating an IKZF2-dependent disease or disorder comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

Another aspect of the present disclosure relates to a method for treating a disease or disorder that is affected by the modulation of IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

In another aspect, the present disclosure relates to a method for treating a disease or disorder that is affected by a decrease in IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

Another aspect of the present disclosure relates to a method for treating a disease or disorder that is affected by the reduction of IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

In another aspect, the present disclosure relates to a method of treating cancer comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the cancer is a cancer for which the immune response is deficient or an immunogenic cancer.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the manufacture of a medicament for treating a disease or disorder associated with the modulation of IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of a disease or disorder associated with the modulation of IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the manufacture of a medicament for treating a disease or disorder associated with the reduction of IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of a disease or disorder associated with the reduction of IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the manufacture of a medicament for treating a disease or disorder associated with a decrease in IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of a disease or disorder associated with a decrease in IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to a method of treating cancer comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the cancer is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of cancer, wherein the cancer is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating cancer, wherein the cancer is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to a method of treating a disease or disorder that is affected by the modulation of IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to a method of treating a disease or disorder that is affected by the reduction of IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to a method of treating a disease or disorder that is affected by a decrease of IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder that is affected by the modulation of IKZF2 protein levels wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder that is affected by the reduction of IKZF2 protein levels wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder that is affected by a decrease of IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a disease or disorder that is affected by the modulation of IKZF2 levels, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

Another aspect of the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a disease or disorder that is affected by the reduction of IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a disease or disorder that is affected by a decrease in IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiforme, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, and Ewing's sarcoma. In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST).

In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).

In another aspect, the present disclosure relates to a method of treating a disease or disorder that is affected by a decrease in IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the disease or disorder is a cancer for which the immune response is deficient or an immunogenic cancer.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder that is affected by the reduction of IKZF2 protein levels, wherein the disease or disorder is a cancer for which the immune response is deficient or an immunogenic cancer.

Another aspect of the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the decrease in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the decrease in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels wherein the decrease in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels wherein the decrease in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels wherein the decrease in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a method of treating a disease or disorder by reducing IKZF2 protein levels comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein reduction of IKZF2 protein levels treats the disease or disorder.

In another aspect, the present disclosure relates to a method of treating a disease or disorder by reducing IKZF2 protein levels comprising the step of administering to a subject in need thereof a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein reduction of IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a method of treating a disease or disorder by modulating IKZF2 protein levels comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein modulation of IKZF2 protein levels treats the disease or disorder.

In another aspect, the present disclosure relates to a method of treating a disease or disorder by modulating IKZF2 protein levels comprising the step of administering to a subject in need thereof a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein modulation of IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a method of treating a disease or disorder by decreasing IKZF2 protein levels comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein decreasing IKZF2 protein levels treats the disease or disorder.

In another aspect, the present disclosure relates to a method of treating a disease or disorder by decreasing IKZF2 protein levels comprising the step of administering to a subject in need thereof a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein decreasing IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels wherein decreasing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels wherein decreasing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder by reducing IKZF2 protein levels, wherein reduction of IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder by modulating IKZF2 protein levels, wherein modulation of IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder by decreasing IKZF2 protein levels, wherein decreasing IKZF2 protein levels treats the disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein reduction of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a IKZF2-dependent disease or disorder by modulating IKZF2 protein levels, wherein modulation of IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a IKZF2-dependent disease or disorder by decreasing IKZF2 protein levels, wherein decreasing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a disease or disorder by reducing IKZF2 protein levels, wherein reduction of IKZF2 protein levels treats the disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a disease or disorder by modulating IKZF2 protein levels, wherein modulation of IKZF2 protein levels treats the disease or disorder.

In another aspect, the present disclosure relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating a disease or disorder by decreasing IKZF2 protein levels, wherein decreasing IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder by reducing IKZF2 protein levels wherein reduction of IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the treatment of a disease or disorder by decreasing IKZF2 protein levels wherein decreasing IKZF2 protein levels treats the disease or disorder.

Another aspect of the present disclosure relates to the use of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of a disease or disorder by decreasing IKZF2 protein levels, wherein decreasing of IKZF2 protein levels treats the disease or disorder.

In another aspect of the disclosure, the compounds according to the disclosure are formulated into pharmaceutical compositions comprising an effective amount, preferably a pharmaceutically effective amount, of a compound according to the disclosure or salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable excipient or carrier.

In some embodiments of the methods disclosed herein, the administration of the compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, is performed orally, parentally, subcutaneously, by injection, or by infusion.

The present disclosure provides degraders of IKZF2 that are therapeutic agents in the treatment of diseases such as cancer and metastasis, in the treatment of diseases affected by the modulation of IKZF2 protein levels, and in the treatment IKZF2-dependent diseases or disorders.

In one embodiment, the disease or disorder that can be treated by the compounds of the present disclosure is selected from prostate cancer, breast carcinoma, lymphomas, leukaemia, myeloma, bladder carcinoma, colon cancer, cutaneous melanoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, cervical cancer, lung cancer, renal cancer, glioblastoma multiform, glioma, thyroid cancer, parathyroid tumor, nasopharyngeal cancer, tongue cancer, pancreatic cancer, esophageal cancer, cholangiocarcinoma, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid cancers, Ewing's sarcoma non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In one embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST). In another embodiment, the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), and microsatellite stable colorectal cancer (mssCRC).In another embodiment, the IKZF2-dependent disease or disorder is a cancer for which the immune response is deficient or an immunogenic cancer.

The present disclosure provides agents with novel mechanisms of action toward IKZF2 proteins in the treatment of various types of diseases including cancer and metastasis, in the treatment of diseases affected by the modulation of IKZF2 protein levels, and in the treatment IKZF2-dependent diseases or disorders. Ultimately the present disclosure provides the medical community with a novel pharmacological strategy for the treatment of diseases and disorders associated with IKZF2 proteins.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure relates to compounds and compositions that are capable of modulating IKZF2 protein levels. The disclosure features methods of treating, preventing, or ameliorating a disease or disorder in which IKZF2 plays a role by administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (I′) or Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. The methods of the present disclosure can be used in the treatment of a variety of IKZF2-dependent diseases and disorders by modulating IKZF2 protein levels. Modulation of IKZF2 protein levels through degradation provides a novel approach to the treatment, prevention, or amelioration of diseases including, but not limited to, cancer and metathesis, and other IKZF2-dependent diseases or disorders.

In one aspect, the compounds of the disclosure have use as therapeutic agents, particularly for cancers and related diseases. In one aspect, the compounds of the disclosure have IKZF2 degradation activity, preferably having such activity at or below the 50 μM level, and more preferably having such activity at or below the 10 μM level. In another aspect, the compounds of the disclosure have degrader activity for IKZF2 that is selective over one or more of IKZF1, IKZF3, IKZF4, and/or IKZF5. In another aspect, the compounds of the disclosure have degrader activity for both IKZF2 and IKZF4. The compounds of the disclosure have usefulness in treating cancer and other diseases for which such degradation activity would be beneficial for the patient. For example, while not intending to be bound by any theory, the inventors believe that reducing levels of IKZF2 in Tregs in a tumor may allow the patient immune system to more effectively attack the disease. In summary, the present disclosure provides novel IKZF2 degraders useful for the treatment of cancer and other diseases.

In a first aspect of the disclosure, the compounds of Formula (I′) are described:

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof, wherein R_x, X₁, X₂, and R₁are as described herein above.

The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, illustrative methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated herein by reference in their entireties.

Definition of Terms and Conventions Used

Terms not specifically defined herein should be given the meanings that would be given to them by one of skill in the art in light of the disclosure and the context. As used in the specification and appended claims, however, unless specified to the contrary, the following terms have the meaning indicated and the following conventions are adhered to.

A. Chemical Nomenclature, Terms, and Conventions

In the groups, radicals, or moieties defined below, the number of carbon atoms is often specified preceding the group, for example, (C₁-C₁₀)alkyl means an alkyl group or radical having 1 to 10 carbon atoms. In general, for groups comprising two or more subgroups, the last named group is the radical attachment point, for example, “alkylaryl” means a monovalent radical of the formula alkyl-aryl-, while “arylalkyl” means a monovalent radical of the formula aryl-alkyl-. Furthermore, the use of a term designating a monovalent radical where a divalent radical is appropriate shall be construed to designate the respective divalent radical and vice versa. Unless otherwise specified, conventional definitions of terms control and conventional stable atom valences are presumed and achieved in all formulas and groups. The articles “a” and “an” refer to one or more than one (e.g., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

The term “and/or” means either “and” or “or” unless indicated otherwise.

The term “optionally substituted” means that a given chemical moiety (e.g., an alkyl group) can (but is not required to) be bonded other substituents (e.g., heteroatoms). For instance, an alkyl group that is optionally substituted can be a fully saturated alkyl chain (e.g., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have substituents different from hydrogen. For instance, it can, at any point along the chain be bounded to a halogen atom, a hydroxyl group, or any other substituent described herein. Thus, the term “optionally substituted” means that a given chemical moiety has the potential to contain other functional groups, but does not necessarily have any further functional groups.

Suitable substituents used in the optional substitution of the described groups include, without limitation, halogen, oxo, —OH, —CN, —COOH, —CH₂CN, —O—(C₁-C₆)alkyl, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, —O—(C₂-C₆)alkenyl, —O—(C₂-C₆)alkynyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, —OH, —OP(O)(OH)₂, —OC(O)(C₁-C₆)alkyl, —C(O)(C₁-C₆)alkyl, —OC(O)O(C₁-C₆)alkyl, —NH₂, —NH((C₁-C₆)alkyl), —N((C₁-C₆)alkyl)₂, —NHC(O)(C₁-C₆)alkyl, —C(O)NH(C₁-C₆)alkyl, —S(O)₂(C₁-C₆)alkyl, —S(O)NH(C₁-C₆)alkyl, and S(O)N((C₁-C₆)alkyl)₂. The substituents can themselves be optionally substituted. “Optionally substituted” as used herein also refers to substituted or unsubstituted whose meaning is described below.

The term “substituted” means that the specified group or moiety bears one or more suitable substituents wherein the substituents may connect to the specified group or moiety at one or more positions. For example, an aryl substituted with a cycloalkyl may indicate that the cycloalkyl connects to one atom of the aryl with a bond or by fusing with the aryl and sharing two or more common atoms.

The term “unsubstituted” means that the specified group bears no substituents.

Unless otherwise specifically defined, “aryl” means a cyclic, aromatic hydrocarbon group having 1 to 3 aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. When containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group are optionally joined at a single point (e.g., biphenyl), or fused (e.g., naphthyl). The aryl group is optionally substituted by one or more substituents, e.g., 1 to 5 substituents, at any point of attachment. Exemplary substituents include, but are not limited to, —H, -halogen, —CN, —O—(C₁-C₆)alkyl, (C₁-C₆)alkyl, —O—(C₂-C₆)alkenyl, —O—(C₂-C₆)alkynyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, —OH, —OP(O)(OH)₂, —OC(O)(C₁-C₆)alkyl, —C(O)(C₁-C₆)alkyl, —OC(O)O(C₁-C₆) alkyl, —NH₂, —NH((C₁-C₆)alkyl), —N((C₁-C₆)alkyl)₂, —S(O)₂—(C₁-C₆)alkyl, —S(O)NH(C₁-C₆)alkyl, and S(O)N((C₁-C₆)alkyl)₂. The substituents are themselves optionally substituted. Furthermore, when containing two fused rings, the aryl groups optionally have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoannulenyl, and the like.

Unless otherwise specifically defined, “heteroaryl” means a monovalent monocyclic aromatic radical of 5 to 24 ring atoms or a polycyclic aromatic radical, containing one or more ring heteroatoms selected from N, O, or S, the remaining ring atoms being C. Heteroaryl as herein defined also means a bicyclic heteroaromatic group wherein the heteroatom is selected from N, O, or S. The aromatic radical is optionally substituted independently with one or more substituents described herein. Examples include, but are not limited to, furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, dihydrobenzoxanyl, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, tetrahydropyrrolo[1,2-a]pyrimidinyl, 3,4-dihydro-2H-1Δ²-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiazinyl, benzooxazolyl, benzoisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazolo[1,5-b][1,2]oxazinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4 d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl, and derivatives thereof. Furthermore, when containing two fused rings the aryl groups herein defined may have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these heteroaryl groups include indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine,3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuran, indolinyl, indolyl, and dihydrobenzoxanyl.

Halogen or “halo” mean fluorine, chlorine, bromine, or iodine.

“Alkyl” means a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms. Examples of a (C₁-C₆)alkyl group include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

“Alkoxy” means a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms containing a terminal “O” in the chain, e.g., —O(alkyl). Examples of alkoxy groups include, without limitation, methoxy, ethoxy, propoxy, butoxy, t-butoxy, or pentoxy groups.

“Alkenyl” means a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The “alkenyl” group contains at least one double bond in the chain. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, isobutenyl, pentenyl, or hexenyl. An alkenyl group can be unsubstituted or substituted and may be straight or branched.

“Alkynyl” means a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The “alkynyl” group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propargyl, n-butynyl, isobutynyl, pentynyl, or hexynyl. An alkynyl group can be unsubstituted or substituted.

“Cycloalkyl” or “carbocyclyl” means a monocyclic or polycyclic saturated carbon ring containing 3-18 carbon atoms. Examples of cycloalkyl groups include, without limitations, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl and derivatives thereof. A (C₃-C₅)cycloalkyl is a cycloalkyl group containing between 3 and 8 carbon atoms. A cycloalkyl group can be fused (e.g., decalin) or bridged (e.g., norbomane).

“Heterocyclyl” or “heterocycloalkyl” means a saturated or partially saturated monocyclic or polycyclic ring containing carbon and at least one heteroatom selected from oxygen, nitrogen, or sulfur (O, N, or S) and wherein there is not delocalized n electrons (aromaticity) shared among the ring carbon or heteroatoms. The heterocycloalkyl ring structure may be substituted by one or more substituents. The substituents can themselves be optionally substituted. Examples of heterocyclyl rings include, but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, oxazolidinonyl, 1,4-dioxanyl, dihydrofuranyl, 1,3-dioxolanyl, imidazolidinyl, imidazolinyl, dithiolanyl, and homotropanyl.

“Haloalkyl” means an alkyl group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, etc.

“Haloalkoxy” means an alkoxy group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, trichloromethoxy, etc.

“Cyano” means a substituent having a carbon atom joined to a nitrogen atom by a triple bond, e.g., C≡N.

“Amino” means a substituent containing at least one nitrogen atom (e.g., —NH₂).

“Hydroxyalkyl” means an alkyl group substituted with one or more —OH groups. Examples of hydroxyalkyl groups include HO—CH₂—, HO—CH₂CH₂—, and CH₂—CH(OH)—.

“Spirocycloalkyl” or “spirocyclyl” means carbogenic bicyclic ring systems with both rings connected through a single atom. The rings can be different in size and nature, or identical in size and nature. Examples include spiropentane, spriohexane, spiroheptane, spirooctane, spirononane, or spirodecane. One or both of the rings in a spirocycle can be fused to another ring carbocyclic, heterocyclic, aromatic, or heteroaromatic ring. A (C₃-C₁₂)spirocycloalkyl is a spirocycle containing between 3 and 12 carbon atoms.

“Spiroheterocycloalkyl” or “spiroheterocyclyl” means a spirocycle wherein at least one of the rings is a heterocycle one or more of the carbon atoms can be substituted with a heteroatom (e.g., one or more of the carbon atoms can be substituted with a heteroatom in at least one of the rings). One or both of the rings in a spiroheterocycle can be fused to another ring carbocyclic, heterocyclic, aromatic, or heteroaromatic ring.

B. Salt, Prodrug, Derivative, and Solvate Terms and Conventions

“Prodrug” or “prodrug derivative” mean a covalently-bonded derivative or carrier of the parent compound or active drug substance which undergoes at least some biotransformation prior to exhibiting its pharmacological effect(s). In general, such prodrugs have metabolically cleavable groups and are rapidly transformed in vivo to yield the parent compound, for example, by hydrolysis in blood, and generally include esters and amide analogs of the parent compounds. The prodrug is formulated with the objectives of improved chemical stability, improved patient acceptance and compliance, improved bioavailability, prolonged duration of action, improved organ selectivity, improved formulation (e.g., increased hydrosolubility), and/or decreased side effects (e.g., toxicity). In general, prodrugs themselves have weak or no biological activity and are stable under ordinary conditions. Prodrugs can be readily prepared from the parent compounds using methods known in the art, such as those described in A Textbook of Drug Design and Development, Krogsgaard-Larsen and H. Bundgaard (eds.), Gordon & Breach, 1991, particularly Chapter 5: “Design and Applications of Prodrugs”; Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985; Prodrugs: Topical and Ocular Drug Delivery, K. B. Sloan (ed.), Marcel Dekker, 1998; Methods in Enzymology, K. Widder et al. (eds.), Vol. 42, Academic Press, 1985, particularly pp. 309-396; Burger's Medicinal Chemistry and Drug Discovery, 5th Ed., M. Wolff (ed.), John Wiley & Sons, 1995, particularly Vol. 1 and pp. 172-178 and pp. 949-982; Pro-Drugs as Novel Delivery Systems, T. Higuchi and V. Stella (eds.), Am. Chem. Soc., 1975; Bioreversible Carriers in Drug Design, E. B. Roche (ed.), Elsevier, 1987, each of which is incorporated herein by reference in their entireties.

“Pharmaceutically acceptable prodrug” as used herein means a prodrug of a compound of the disclosure which is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible.

“Salt” means an ionic form of the parent compound or the product of the reaction between the parent compound with a suitable acid or base to make the acid salt or base salt of the parent compound. Salts of the compounds of the present disclosure can be synthesized from the parent compounds, which contain a basic or acidic moiety, by conventional chemical methods. Generally, the salts are prepared by reacting the free base or acid parent compound with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid or base in a suitable solvent or various combinations of solvents.

“Pharmaceutically acceptable salt” means a salt of a compound of the disclosure which is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, generally water or oil-soluble or dispersible, and effective for their intended use. The term includes pharmaceutically-acceptable acid addition salts and pharmaceutically-acceptable base addition salts. As the compounds of the present disclosure are useful in both free base and salt form, in practice, the use of the salt form amounts to use of the base form. Lists of suitable salts are found in, e.g., S. M. Birge et al., J. Pharm. Sci., 1977, 66, pp. 1-19, which is hereby incorporated by reference in its entirety.

“Pharmaceutically-acceptable acid addition salt” means those salts which retain the biological effectiveness and properties of the free bases and which are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, nitric acid, phosphoric acid, and the like, and organic acids such as acetic acid, trichloroacetic acid, trifluoroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 2-acetoxybenzoic acid, butyric acid, camphoric acid, camphorsulfonic acid, cinnamic acid, citric acid, digluconic acid, ethanesulfonic acid, glutamic acid, glycolic acid, glycerophosphoric acid, hemisulfic acid, heptanoic acid, hexanoic acid, formic acid, fumaric acid, 2-hydroxyethanesulfonic acid (isethionic acid), lactic acid, maleic acid, hydroxymaleic acid, malic acid, malonic acid, mandelic acid, mesitylenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, pamoic acid, pectinic acid, phenylacetic acid, 3-phenylpropionic acid, picric acid, pivalic acid, propionic acid, pyruvic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, tartaric acid, p-toluenesulfonic acid, undecanoic acid, and the like.

“Pharmaceutically-acceptable base addition salt” means those salts which retain the biological effectiveness and properties of the free acids and which are not biologically or otherwise undesirable, formed with inorganic bases such as ammonia or hydroxide, carbonate, or bicarbonate of ammonium or a metal cation such as sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Particularly preferred are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically-acceptable organic nontoxic bases include salts of primary, secondary, and tertiary amines, quaternary amine compounds, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins, such as methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, TEA, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tetramethylammonium compounds, tetraethylammonium compounds, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine, N,N′-dibenzylethylenediamine, polyamine resins, and the like. Particularly preferred organic nontoxic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

“Solvate” means a complex of variable stoichiometry formed by a solute, for example, a compound of Formula (I′) or Formula (I)) and solvent, for example, water, ethanol, or acetic acid. This physical association may involve varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. In general, such solvents selected for the purpose of the disclosure do not interfere with the biological activity of the solute. Solvates encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, methanolates, and the like.

“Hydrate” means a solvate wherein the solvent molecule(s) is/are water.

The compounds of the present disclosure as discussed below include the free base or acid thereof, their salts, solvates, and prodrugs and may include oxidized sulfur atoms or quaternized nitrogen atoms in their structure, although not explicitly stated or shown, particularly the pharmaceutically acceptable forms thereof. Such forms, particularly the pharmaceutically acceptable forms, are intended to be embraced by the appended claims.

C. Isomer Terms and Conventions

“Isomers” means compounds having the same number and kind of atoms, and hence the same molecular weight, but differing with respect to the arrangement or configuration of the atoms in space. The term includes stereoisomers and geometric isomers.

“Stereoisomer” or “optical isomer” mean a stable isomer that has at least one chiral atom or restricted rotation giving rise to perpendicular dissymmetric planes (e.g., certain biphenyls, allenes, and spiro compounds) and can rotate plane-polarized light. Because asymmetric centers and other chemical structure exist in the compounds of the disclosure, which may give rise to stereoisomerism, the disclosure contemplates stereoisomers and mixtures thereof. The compounds of the disclosure and their salts include asymmetric carbon atoms and may therefore exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. Typically, such compounds will be prepared as a racemic mixture. If desired, however, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures. As discussed in more detail below, individual stereoisomers of compounds are prepared by synthesis from optically active starting materials containing the desired chiral centers or by preparation of mixtures of enantiomeric products followed by separation or resolution, such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, use of chiral resolving agents, or direct separation of the enantiomers on chiral chromatographic columns. Starting compounds of particular stereochemistry are either commercially available or are made by the methods described below and resolved by techniques well-known in the art.

“Enantiomers” means a pair of stereoisomers that are non-superimposable mirror images of each other.

“Diastereoisomers” or “diastereomers” mean optical isomers which are not mirror images of each other.

“Racemic mixture” or “racemate” mean a mixture containing equal parts of individual enantiomers.

“Non-racemic mixture” means a mixture containing unequal parts of individual enantiomers.

“Geometrical isomer” means a stable isomer which results from restricted freedom of rotation about double bonds (e.g., cis-2-butene and trans-2-butene) or in a cyclic structure (e.g., cis-1,3-dichlorocyclobutane and trans-1,3-dichlorocyclobutane). Because carbon-carbon double (olefinic) bonds, C═N double bonds, cyclic structures, and the like may be present in the compounds of the disclosure, the disclosure contemplates each of the various stable geometric isomers and mixtures thereof resulting from the arrangement of substituents around these double bonds and in these cyclic structures. The substituents and the isomers are designated using the cis/trans convention or using the E or Z system, wherein the term “E” means higher order substituents on opposite sides of the double bond, and the term “Z” means higher order substituents on the same side of the double bond. A thorough discussion of E and Z isomerism is provided in J. March, Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed., John Wiley & Sons, 1992, which is hereby incorporated by reference in its entirety. Several of the following examples represent single E isomers, single Z isomers, and mixtures of E/Z isomers. Determination of the E and Z isomers can be done by analytical methods such as x-ray crystallography, ¹H NMR, and ¹³C NMR.

Some of the compounds of the disclosure can exist in more than one tautomeric form. As mentioned above, the compounds of the disclosure include all such tautomers.

It is well-known in the art that the biological and pharmacological activity of a compound is sensitive to the stereochemistry of the compound. Thus, for example, enantiomers often exhibit strikingly different biological activity including differences in pharmacokinetic properties, including metabolism, protein binding, and the like, and pharmacological properties, including the type of activity displayed, the degree of activity, toxicity, and the like. Thus, one skilled in the art will appreciate that one enantiomer may be more active or may exhibit beneficial effects when enriched relative to the other enantiomer or when separated from the other enantiomer. Additionally, one skilled in the art would know how to separate, enrich, or selectively prepare the enantiomers of the compounds of the disclosure from this disclosure and the knowledge of the prior art.

Thus, although the racemic form of drug may be used, it is often less effective than administering an equal amount of enantiomerically pure drug; indeed, in some cases, one enantiomer may be pharmacologically inactive and would merely serve as a simple diluent. For example, although ibuprofen had been previously administered as a racemate, it has been shown that only the S-isomer of ibuprofen is effective as an anti-inflammatory agent (in the case of ibuprofen, however, although the R-isomer is inactive, it is converted in vivo to the S-isomer, thus, the rapidity of action of the racemic form of the drug is less than that of the pure S-isomer). Furthermore, the pharmacological activities of enantiomers may have distinct biological activity. For example, S-penicillamine is a therapeutic agent for chronic arthritis, while R-penicillamine is toxic. Indeed, some purified enantiomers have advantages over the racemates, as it has been reported that purified individual isomers have faster transdermal penetration rates compared to the racemic mixture. See U.S. Pat. Nos. 5,114,946 and 4,818,541.

Thus, if one enantiomer is pharmacologically more active, less toxic, or has a preferred disposition in the body than the other enantiomer, it would be therapeutically more beneficial to administer that enantiomer preferentially. In this way, the patient undergoing treatment would be exposed to a lower total dose of the drug and to a lower dose of an enantiomer that is possibly toxic or an inhibitor of the other enantiomer.

Preparation of pure enantiomers or mixtures of desired enantiomeric excess (ee) or enantiomeric purity are accomplished by one or more of the many methods of (a) separation or resolution of enantiomers, or (b) enantioselective synthesis known to those of skill in the art, or a combination thereof. These resolution methods generally rely on chiral recognition and include, for example, chromatography using chiral stationary phases, enantioselective host-guest complexation, resolution or synthesis using chiral auxiliaries, enantioselective synthesis, enzymatic and nonenzymatic kinetic resolution, or spontaneous enantioselective crystallization. Such methods are disclosed generally in Chiral Separation Techniques: A Practical Approach (2nd Ed.), G. Subramanian (ed.), Wiley-VCH, 2000; T. E. Beesley and R. P. W. Scott, Chiral Chromatography, John Wiley & Sons, 1999; and Satinder Ahuja, Chiral Separations by Chromatography, Am. Chem. Soc., 2000. Furthermore, there are equally well-known methods for the quantitation of enantiomeric excess or purity, for example, GC, HPLC, CE, or NMR, and assignment of absolute configuration and conformation, for example, CD ORD, X-ray crystallography, or NMR.

In general, all tautomeric forms and isomeric forms and mixtures, whether individual geometric isomers or stereoisomers or racemic or non-racemic mixtures, of a chemical structure or compound is intended, unless the specific stereochemistry or isomeric form is specifically indicated in the compound name or structure.

D. Pharmaceutical Administration and Treatment Terms and Conventions

A “patient” or “subject” is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or nonhuman primate, such as a monkey, chimpanzee, baboon or, rhesus. In certain embodiments, the subject is a primate. In yet other embodiments, the subject is a human.

An “effective amount” or “therapeutically effective amount” when used in connection with a compound means an amount of a compound of the present disclosure that (i) treats or prevents the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein.

The terms “pharmaceutically effective amount” or “therapeutically effective amount” means an amount of a compound according to the disclosure which, when administered to a patient in need thereof, is sufficient to effect treatment for disease-states, conditions, or disorders for which the compounds have utility. Such an amount would be sufficient to elicit the biological or medical response of a tissue, system, or patient that is sought by a researcher or clinician. The amount of a compound of according to the disclosure which constitutes a therapeutically effective amount will vary depending on such factors as the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of treatment, the type of disease-state or disorder being treated and its severity, drugs used in combination with or coincidentally with the compounds of the disclosure, and the age, body weight, general health, sex, and diet of the patient. Such a therapeutically effective amount can be determined routinely by one of ordinary skill in the art having regard to their own knowledge, the prior art, and this disclosure.

As used herein, the term “pharmaceutical composition” refers to a compound of the disclosure, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, together with at least one pharmaceutically acceptable carrier, in a form suitable for oral or parenteral administration.

“Carrier” encompasses carriers, excipients, and diluents and means a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body of a subject.

A subject is “in need of” a treatment if such subject would benefit biologically, medically, or in quality of life from such treatment (preferably, a human).

As used herein, the term “inhibit”, “inhibition”, or “inhibiting” refers to the reduction or suppression of a given condition, symptom, or disorder, or disease, or a significant decrease in the baseline activity of a biological activity or process.

As used herein, the term “treat”, “treating”, or “treatment” of any disease or disorder refers to alleviating or ameliorating the disease or disorder (i.e., slowing or arresting the development of the disease or at least one of the clinical symptoms thereof); or alleviating or ameliorating at least one physical parameter or biomarker associated with the disease or disorder, including those which may not be discernible to the patient.

As used herein, the term “prevent”, “preventing”, or “prevention” of any disease or disorder refers to the prophylactic treatment of the disease or disorder; or delaying the onset or progression of the disease or disorder.

“Pharmaceutically acceptable” means that the substance or composition must be compatible chemically and/or toxicologically, with the other ingredients comprising a formulation, and/or the mammal being treated therewith.

“Disorder” means, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise indicated.

“Administer”, “administering”, or “administration” means to either directly administering a disclosed compound or pharmaceutically acceptable salt of the disclosed compound or a composition to a subject, or administering a prodrug derivative or analog of the compound or pharmaceutically acceptable salt of the compound or composition to the subject, which can form an equivalent amount of active compound within the subject's body.

“Prodrug” means a compound which is convertible in vivo by metabolic means (e.g., by hydrolysis) to a disclosed compound.

“Compounds of the present disclosure”, “Compounds of Formula (I′) or Formula (I)”, “compounds of the disclosure”, and equivalent expressions (unless specifically identified otherwise) refer to compounds of Formulae (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im) (In), (Io), (Ip), (Iq), (Ir), (Is), and (It) as herein described including the tautomers, the prodrugs, salts particularly the pharmaceutically acceptable salts, and the solvates and hydrates thereof, where the context so permits thereof, as well as all stereoisomers (including diastereoisomers and enantiomers), rotamers, tautomers, and isotopically labelled compounds (including deuterium substitutions), as well as inherently formed moieties (e.g., polymorphs, solvates and/or hydrates). For purposes of this disclosure, solvates and hydrates are generally considered compositions. In general and preferably, the compounds of the disclosure and the formulas designating the compounds of the disclosure are understood to only include the stable compounds thereof and exclude unstable compounds, even if an unstable compound might be considered to be literally embraced by the compound formula. Similarly, reference to intermediates, whether or not they themselves are claimed, is meant to embrace their salts and solvates, where the context so permits. For the sake of clarity, particular instances when the context so permits are sometimes indicated in the text, but these instances are purely illustrative and it is not intended to exclude other instances when the context so permits.

“Stable compound” or “stable structure” means a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic or diagnostic agent. For example, a compound that would have a “dangling valency” or is a carbanion is not a compound contemplated by the disclosure.

In a specific embodiment, the term “about” or “approximately” means within 20%, preferably within 10%, and more preferably within 5% of a given value or range.

The yield of each of the reactions described herein is expressed as a percentage of the theoretical yield. “Cancer” means any cancer caused by the proliferation of malignant neoplastic cells, such as tumors, neoplasms, carcinomas, sarcomas, leukemias, lymphomas, and the like. For example, cancers include, but are not limited to, mesothelioma, leukemias, and lymphomas such as cutaneous T-cell lymphomas (CTCL), noncutaneous peripheral T-cell lymphomas, lymphomas associated with human T-cell lymphotrophic virus (HTLV) such as adult T-cell leukemia/lymphoma (ATLL), B-cell lymphoma, acute nonlymphocytic leukemias, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, lymphomas, and multiple myeloma, non-Hodgkin lymphoma, acute lymphatic leukemia (ALL), chronic lymphatic leukemia (CLL), Hodgkin's lymphoma, Burkitt lymphoma, adult T-cell leukemia lymphoma, acute-myeloid leukemia (AML), chronic myeloid leukemia (CML), or hepatocellular carcinoma. Further examples include myelodisplastic syndrome, childhood solid tumors such as brain tumors, neuroblastoma, retinoblastoma, Wilms' tumor, bone tumors, and soft-tissue sarcomas, common solid tumors of adults such as head and neck cancers (e.g., oral, laryngeal, nasopharyngeal, and esophageal), genitourinary cancers (e.g., prostate, bladder, renal, uterine, ovarian, testicular), lung cancer (e.g., small-cell and non-small cell), breast cancer (e.g., triple-negative breast cancer (TNBC)), pancreatic cancer, melanoma, and other skin cancers, stomach cancer, brain tumors, tumors related to Gorlin's syndrome (e.g., medulloblastoma, meningioma, etc.), and liver cancer. Additional exemplary forms of cancer which may be treated by the subject compounds include, but are not limited to, cancer of skeletal or smooth muscle, stomach cancer, cancer of the small intestine, rectum carcinoma, cancer of the salivary gland, endometrial cancer, adrenal cancer, anal cancer, rectal cancer, parathyroid cancer, and pituitary cancer.

Additional cancers that the compounds described herein may be useful in preventing, treating, and studying are, for example, colon carcinoma, familiary adenomatous polyposis carcinoma, and hereditary non-polyposis colorectal cancer, or melanoma. Further, cancers include, but are not limited to, labial carcinoma, larynx carcinoma, hypopharynx carcinoma, tongue carcinoma, salivary gland carcinoma, gastric carcinoma, adenocarcinoma, thyroid cancer (medullary and papillary thyroid carcinoma), renal carcinoma, kidney parenchyma carcinoma, cervix carcinoma, uterine corpus carcinoma, endometrium carcinoma, chorion carcinoma, testis carcinoma, urinary carcinoma, melanoma, brain tumors such as glioblastoma, astrocytoma, meningioma, medulloblastoma and peripheral neuroectodermal tumors, gall bladder carcinoma, bronchial carcinoma, multiple myeloma, basalioma, teratoma, retinoblastoma, choroidea melanoma, seminoma, rhabdomyosarcoma, craniopharyngeoma, osteosarcoma, chondrosarcoma, myosarcoma, liposarcoma, fibrosarcoma, Ewing's sarcoma, plasmocytoma, non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myelogenous leukemia, and gastrointestinal stromal tumor (GIST).

“Simultaneously” or “simultaneous” when referring to a method of treating or a therapeutic use means with a combination of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one or more second agent(s) means administration of the compound and the one or more second agent(s) by the same route and at the same time.

“Separately” or “separate” when referring to a method of treating or a therapeutic use means with a combination of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one or more second agent(s) means administration of the compound and the one or more second agent(s) by different routes and at approximately the same time.

By therapeutic administration “over a period of time” means, when referring to a method of treating or a therapeutic use with a combination of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one or more second agent(s), administration of the compound and the one or more second agent(s) by the same or different routes and at different times. In some embodiments, the administration of the compound or the one or more second agent(s) occurs before the administration of the other begins. In this way, it is possible to administer a one of the active ingredients (i.e., a compound of the Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or one or more second agent(s)) for several months before administering the other active ingredient or ingredients. In this case, no simultaneous administration occurs. Another therapeutic administration over a period of time consists of the administration over time of the two or more active ingredients of the combination using different frequencies of administration for each of the active ingredients, whereby at certain time points in time simultaneous administration of all of the active ingredients takes place whereas at other time points in time only a part of the active ingredients of the combination may be administered (e.g., for example. a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and the one or more second agents the therapeutic administration over a period of time could be such that a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, is administered once a day and the one or more second agent(s) is administered once every four weeks.)

“IKZF2-dependent disease or disorder” means any disease or disorder which is directly or indirectly affected by the modulation of IKZF2 protein levels.

“IKZF4-dependent disease or disorder” means any disease or disorder which is directly or indirectly affected by the modulation of IKZF4 protein levels.

D. Specific Embodiments and Methods for Testing Compounds of Formula (I′) or Formula (I)

The present disclosure relates to compounds or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof, capable of modulating IKZF2 protein levels, which are useful for the treatment of diseases and disorders associated with modulation of IKZF2 protein levels.

The disclosure further relates to compounds, or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof, which are useful for reducing or decreasing IKZF2 protein levels.

In one embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ia):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ib):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In yet another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ic):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Id):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ie):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (If):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ig):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ih):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ii)

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ij):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ik):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Il):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Im):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (In):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Io):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ip):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Iq):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Ir):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (Is):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In another embodiment, the compounds of Formula (I′) or Formula (I) have the structure of Formula (It):

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or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

In some embodiments of the formulae above (e.g., Formulae (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (p), (Iq), (Ir), (Is), and (It)), R₁is

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In another embodiment, R₁is

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In some embodiments of the formulae above, X₁is H, (C₁-C₃)alkyl, (C₁-C₆)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₆)haloalkoxy, (C₃-C₇)cycloalkyl, halogen, —CN, —OH, or —NH₂. In another embodiment, X₁is H, (C₁-C₃)alkyl, (C₁-C₆)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₃)haloalkoxy, halogen, —CN, —OH, or —NH₂. In yet another embodiment, X₁is H, (C₁-C₄)alkyl, (C₁-C₆)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, (C₃-C₇)cycloalkyl, or halogen. In another embodiment, X₁is H, (C₁-C₄)alkyl, (C₁-C₆)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, or halogen. In yet another embodiment, X₁is H, halogen, —CN, —OH, or —NH₂. In another embodiment, X₁is H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, halogen, —CN, —OH, or —NH₂. In yet another embodiment, X₁is H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, halogen, —OH, or —NH₂. In another embodiment, X₁is H, (C₁-C₄)alkyl, halogen, —OH, or —NH₂. In yet another embodiment, X₁is H, halogen, —OH, or —NH₂. In another embodiment, X₁is H.

In some embodiments of the formulae above, X₂is H, (C₁-C₃)alkyl, (C₁-C₆)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₆)haloalkoxy, (C₃-C₇)cycloalkyl, halogen, —CN, —OH, or —NH₂. In another embodiment, X₂is H, (C₁-C₃)alkyl, (C₁-C₆)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₃)haloalkoxy, halogen, —CN, —OH, or —NH₂. In yet another embodiment, X₂is H, (C₁-C₄)alkyl, (C₁-C₆)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, (C₃-C₇)cycloalkyl, or halogen. In another embodiment, X₂is H, (C₁-C₄)alkyl, (C₁-C₆)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, or halogen. In yet another embodiment, X₂is H, halogen, —CN, —OH, or —NH₂. In another embodiment, X₂is H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, halogen, —CN, —OH, or —NH₂. In yet another embodiment, X₂is H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, halogen, —OH, or —NH₂. In another embodiment, X₂is H, (C₁-C₄)alkyl, halogen, —OH, or —NH₂. In yet another embodiment, X₂is H, halogen, —OH, or —NH₂. In another embodiment, X₂is H.

In some embodiments of the formulae above, X₁is H and X₂is (C₁-C₃)alkyl, (C₁-C₆)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₆)haloalkoxy, (C₃-C₇)cycloalkyl, halogen, —CN, —OH, or —NH₂. In another embodiment, X₁is (C₁-C₃)alkyl, (C₁-C₆)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₆)haloalkoxy, (C₃-C₇)cycloalkyl, halogen, —CN, —OH, or —NH₂and X₂is H. In yet another embodiment, X₁is H and X₂is H.

In some embodiments of the formulae above, R_xis D. In another embodiment, R_xis H.

In some embodiments of the formulae above, each R₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₃)haloalkoxy, halogen, —CN, —OH, or —NH₂. In another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₃)haloalkoxy, or halogen. In yet another embodiment, R₂is independently at each occurrence halogen, —CN, —OH, or —NH₂. In another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)alkoxy, (C₁-C₃)haloalkyl, or (C₁-C₃)haloalkoxy. In yet another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, halogen, —CN, —OH, or —NH₂. In another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, halogen, or —CN. In yet another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl, halogen, or —CN. In another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl or (C₁-C₃)haloalkyl. In yet another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl or —CN. In another embodiment, R₂is independently at each occurrence (C₁-C₃)alkyl. In yet another embodiment, R₂is independently at each occurrence methyl, ethyl, n-propyl, or isopropyl.

In some embodiments of the formulae above, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 5- or 6-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 5- or 6-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- or 6-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₄-C₇)cycloalkyl. In yet another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₅-C₇)cycloalkyl. In another embodiment, two R₂together with the carbon atoms to which they are attached form a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together when on adjacent carbon atoms form a phenyl or a 5-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R₂together when on adjacent carbon atoms form a phenyl or a 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together when on adjacent carbon atoms form a phenyl. In yet another embodiment, two R₂together when on adjacent carbon atoms form a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together when on adjacent carbon atoms form a 5-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R₂together when on adjacent carbon atoms form a 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl, or two R₂together when on adjacent carbon atoms a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R₂together with the carbon atoms to which they are attached form a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, or two R₂together when on adjacent carbon atoms a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, or two R₂together when on adjacent carbon atoms a phenyl. In yet another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, or two R₂together when on adjacent carbon atoms a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or two R₂together when on adjacent carbon atoms form a phenyl. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₄-C₇)cycloalkyl or two R₂together when on adjacent carbon atoms form a phenyl. In another embodiment, two R₂together with the carbon atoms to which they are attached form a (C₅-C₇)cycloalkyl or two R₂together when on adjacent carbon atoms form a phenyl.

In another embodiment, two R₂together with the carbon atoms to which they are attached form a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or two R₂together when on adjacent carbon atoms form a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R₂together with the carbon atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or two R₂together when on adjacent carbon atoms form a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₂together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or two R₂together when on adjacent carbon atoms form a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen.

In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, each R₃is (C₁-C₆)alkyl, (C₁-C₃)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₃)haloalkoxy, halogen, —OH, or —NH₂. In another embodiment, R₃is (C₁-C₆)alkyl, (C₁-C₃)alkoxy, (C₁-C₃)haloalkyl, (C₁-C₃)haloalkoxy, or halogen. In another embodiment, R₃is (C₁-C₆)alkyl, (C₁-C₃)alkoxy, (C₁-C₃)haloalkyl, or (C₁-C₃)haloalkoxy. In another embodiment, R₃is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, or halogen. In another embodiment, R₃is halogen, —OH, or —NH₂. In another embodiment, R₃is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, halogen, —OH, or —NH₂. In another embodiment, R₃is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, halogen, or —OH. In another embodiment, R₃is (C₁-C₆)alkyl or (C₁-C₃)haloalkyl. In another embodiment, R₃is (C₁-C₆)alkyl.

In some embodiments of the formulae above, R₄is —OR₅. In another embodiment, R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₅is H, (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₅is (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, R₅is H, (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₅is (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, R₅is H, (C₁-C₃)alkyl, or (C₁-C₃)haloalkyl, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₅is (C₁-C₆)alkyl, or (C₁-C₃)haloalkyl, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₅is (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, R₅is H, (C₁-C₃)alkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₅is H, (C₁-C₃)alkyl, (C₃-C₇)cycloalkyl, or 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, R₅is H, (C₁-C₃)alkyl, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₅is H, (C₁-C₃)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, R₅is H, (C₁-C₃)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl. In yet another embodiment, R₅is H, (C₁-C₃)alkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₅is H, (C₁-C₃)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₆is H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In yet another embodiment, R₆is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂.

In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R₆is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇.

In another embodiment, R₆is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In yet another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one to four R₁₂. In yet another embodiment, R₆is H, (C₁-C₆)alkyl, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the aryl and heteroaryl are optionally substituted with one to four R₁₂.

In another embodiment, R₆is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇. In yet another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R₆is H, (C₁-C₆)alkyl, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇.

In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₂-C₆)hydroxyalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the heterocycloalkyl and heteroaryl are optionally substituted with one to four R₁₂. In yet another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl and aryl are optionally substituted with one to four R₁₂. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl and aryl are optionally substituted with one to four R₁₂.

In another embodiment, R₆is H, (C₁-C₆)alkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R₆is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇.

In some embodiments of the formulae above, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In yet another embodiment, R_6′ is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂.

In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R_6′ is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇.

In another embodiment, R_6′ is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In yet another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R₁₂. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, or 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one to four R₁₂. In yet another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₂-C₆)hydroxyalkyl, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the aryl and heteroaryl are optionally substituted with one to four R₁₂.

In another embodiment, R_6′ is (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is substituted with one to three R₇. In yet another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇.

In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₂-C₆)hydroxyalkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇and wherein the heterocycloalkyl and heteroaryl are optionally substituted with one to four R₁₂. In yet another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₂-C₆)hydroxyalkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl and aryl are optionally substituted with one to four R₁₂. In another embodiment, R₆is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇and wherein the cycloalkyl and aryl are optionally substituted with one to four R₁₂. In yet another embodiment, R_6′ is H or (C₁-C₆)alkyl, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R_6′ is H or (C₁-C₆)alkyl, wherein the alkyl is substituted with one to three R₇. In yet another embodiment, R₆is H or (C₁-C₆)alkyl.

In another embodiment, R_6′ is H, (C₁-C₆)alkyl, 5- or 6-membered heterocycloalkyl comprising 1-3 heteroatoms selected from O, N, and S, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₁-C₃)haloalkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R_6′ is H, (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, or (C₆-C₁₀)aryl, wherein the alkyl is optionally substituted with one to three R₇. In yet another embodiment, R_6′ is H or (C₁-C₆)alkyl, wherein the alkyl is optionally substituted with one to three R₇. In another embodiment, R_6′ is H or (C₁-C₆)alkyl, wherein the alkyl is substituted with one to three R₇. In yet another embodiment, R₆is H or (C₁-C₆)alkyl.

In some embodiments of the formulae above, R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. R₆and R_6′ together with the nitrogen atom to which they are attached form a 6- to 8-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. R₆and R_6′ together with the nitrogen atom to which they are attached form a 7- or 8-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In yet another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- or 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In yet another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈.

In another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 6- or 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In yet another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 4-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In another embodiment, R₆and R_6′together with the nitrogen atom to which they are attached form a 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In yet another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈. In another embodiment, R₆and R_6′ together with the nitrogen atom to which they are attached form a 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three R₈.

In some embodiments of the formulae above, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂. In yet another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen.

In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In yet another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 5-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S.

In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In yet another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, substituted with one to four substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, and halogen. In another embodiment, R₂and R₆together with the carbon and nitrogen atoms to which they are attached form a 6-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, each R₇is (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to three R₉. In another embodiment, each R₇is (C₃-C₇)cycloalkyl or 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one to three R₉. In yet another embodiment, each R₇is (C₆-C₁₀)aryl or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl are optionally substituted with one to three R₉.

In another embodiment, each R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one to three R₉. In yet another embodiment, each R₇is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the heterocycloalkyl and heteroaryl are optionally substituted with one to three R₉. In another embodiment, each R₇is (C₃-C₇)cycloalkyl or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the cycloalkyl and heteroaryl are optionally substituted with one to three R₉. In yet another embodiment, each R₇is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or (C₆-C₁₀)aryl, wherein the heterocycloalkyl and aryl are optionally substituted with one to three R₉.

In another embodiment, each R₇is (C₃-C₇)cycloalkyl optionally substituted with one to three R₉. In yet another embodiment, each R₇is (C₃-C₇)cycloalkyl substituted with one to three R₉. In another embodiment, each R₇is (C₃-C₇)cycloalkyl. In yet another embodiment, each R₇is (C₆-C₁₀)aryl optionally substituted with one to three R₉. In another embodiment, each R₇is (C₆-C₁₀)aryl substituted with one to three R₉. In yet another embodiment, each R₇is (C₆-C₁₀)aryl.

In another embodiment, each R₇is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, optionally substituted with one to three R₉. In yet another embodiment, each R₇is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, substituted with one to three R₉. In another embodiment, each R₇is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R₇is 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, optionally substituted with one to three R₉. In another embodiment, each R₇is 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, substituted with one to three R₉. In yet another embodiment, each R is 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, each R is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, —CN, —OH, —NR₁₃R₁₄, —NH₂, —O(C₃-C₇)cycloalkyl, —O-4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, —O(C₆-C₁₀)aryl, or —O-5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkoxy is optionally substituted with one to three R₁₀and the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one to three R₁₁. In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, —CN, —OH, —NR₁₃R₁₄, and —NH₂. In another embodiment, each R₈is independently at each occurrence —NR₁₃R₁₄, —NH₂, —O(C₃-C₇)cycloalkyl, —O-4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, —O(C₆-C₁₀)aryl, or —O-5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, —CN, —OH, —NR₁₃R₁₄, —O(C₃-C₇)cycloalkyl, —O-4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, —O(C₆-C₁₀)aryl, or —O-5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, wherein the alkoxy is optionally substituted with one or two R₁₀and the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one to three R₁₁.

In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, —CN, —OH, or —NH₂, wherein the alkoxy is optionally substituted with one to three substituents independently selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, —CN, or —OH, wherein the alkoxy is optionally substituted with one to three substituents independently selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, halogen, —CN, or —OH, wherein the alkoxy is optionally substituted with (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, and (C₆-C₁₀)aryl.

In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, halogen, —CN, or —OH, wherein the alkoxy is optionally substituted with one to three substituents independently selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, halogen, —CN, or —OH, wherein the alkoxy is optionally substituted with one to three substituents independently selected from (C₃-C₇)cycloalkyl, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₈is independently at each occurrence halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₄)haloalkoxy, halogen, —CN, or —OH, wherein the alkoxy is optionally substituted with one to three substituents independently selected from 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, each R₈is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, halogen, —CN, —OH, or —NH₂. In another embodiment, each R₈is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —CN, —OH, or —NH₂. In yet another embodiment, each R₈is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, or halogen. In another embodiment, each R₈is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, or —OH. In yet another embodiment, each R₈is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, or —NH₂.

In another embodiment, each R₈is independently at each occurrence halogen, —CN, —OH, or —NH₂. In yet another embodiment, each R₈is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or halogen. In another embodiment, each R₈is independently at each occurrence (C₁-C₆)alkyl or halogen. In another embodiment, each R₈is independently at each occurrence (C₁-C₆)alkyl, halogen, or —CN. In yet another embodiment, each R₈is independently at each occurrence halogen or —CN. In yet another embodiment, each R₈is independently at each occurrence halogen.

In some embodiments of the formulae above, two R₈together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₄-C₆)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₄-C₆)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl or a 6- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl or a 4- to 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅.

In another embodiment, two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl. In yet another embodiment, two R₈together with the atoms to which they are attached form a (C₅-C₆)cycloalkyl. In another embodiment, two R₈together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl. In yet another embodiment, two R₈together with the atoms to which they are attached form a (C₅)cycloalkyl. In another embodiment, two R₈together with the atoms to which they are attached form a (C₆)cycloalkyl. In yet another embodiment, two R₈together with the atoms to which they are attached form a (C₇)cycloalkyl.

In another embodiment, two R₈together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a (C₅-C₆)cycloalkyl optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a (C₅)cycloalkyl optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a (C₆)cycloalkyl optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a (C₇)cycloalkyl optionally substituted with two R₁₅.

In another embodiment, two R₈together with the atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R₈together with the atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₈together with the atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R₈together with the atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₈together with the atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R₈together with the atoms to which they are attached form a 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₈together with the atoms to which they are attached form a 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R₈together with the atoms to which they are attached form a 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In another embodiment, two R₈together with the atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈together with the atoms to which they are attached form a 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In yet another embodiment, two R₈together with the atoms to which they are attached form a 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅.

In another embodiment, two R₈when on the same carbon atom together with the atoms to which they are attached form a (C₄-C₇)spirocycloalkyl or a 4- to 7-membered spiroheterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅. In another embodiment, two R₈when on adjacent atoms together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with two R₁₅.

In another embodiment, two R₈when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₈when on adjacent atoms together with the atoms to which they are attached form a phenyl or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₈when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl. In another embodiment, two R₈when on adjacent atoms together with the atoms to which they are attached form a 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₈when on adjacent atoms together with the atoms to which they are attached form a phenyl.

In another embodiment, two R₈together with the same atom to which they are attached form a ═(O).

In some embodiments of the formulae above, each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, (C₃-C₆)cycloalkyl, —OH, —CN, —NH₂, or —NR₁₃R₁₄. In another embodiment, R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, (C₃-C₆)cycloalkyl, —OH, —CN, or NR₁₃R₁₄. In another embodiment, each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, or —NH₂. In another embodiment, each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, or —CN. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, halogen, or —CN. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, halogen, or —CN. In yet another embodiment, each R₉is independently at each occurrence halogen, —OH, —CN, or —NH₂. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, or halogen. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, or halogen. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or halogen. In yet another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or —CN. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl or (C₁-C₃)haloalkyl. In yet another embodiment, each R₉is independently at each occurrence halogen or —CN. In another embodiment, each R₉is independently at each occurrence (C₁-C₃)alkyl or halogen. In yet another embodiment, each R₉is independently at each occurrence (C₁-C₃)haloalkyl.

In some embodiments of the formulae above, two R₉together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂. In another embodiment, two R₉together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂. In another embodiment, two R₉together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one to three substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, and —CN. In another embodiment, two R₉together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one to three halogen. In yet another embodiment, two R₉together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₉together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl. In another embodiment, two R₉together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl. In another embodiment, two R₉together with the atoms to which they are attached form a (C₅-C₆)cycloalkyl. In yet another embodiment, two R₉together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl. In another embodiment, two R₉together with the atoms to which they are attached form a (C₄)cycloalkyl. In another embodiment, two R₉together with the atoms to which they are attached form a (C₅)cycloalkyl. In yet another embodiment, two R₉together with the atoms to which they are attached form a (C₆)cycloalkyl. In another embodiment, two R₉together with the atoms to which they are attached form a (C₇)cycloalkyl.

In another embodiment, two R₉together with the atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₉together with the atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₉together with the atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₉together with the atoms to which they are attached form a 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₉together with the atoms to which they are attached form a 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₉together with the atoms to which they are attached form a 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a phenyl or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl or 5-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a phenyl or 5-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a phenyl. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a 5-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R₉when on adjacent atoms together with the atoms to which they are attached form a 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, each R₁₀is (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₁₀is (C₃-C₇)cycloalkyl or 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R₁₀is (C₆-C₁₀)aryl or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S

In another embodiment, each R₁₀is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl. In yet another embodiment, each R₁₀is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₁₀is (C₃-C₇)cycloalkyl or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R₁₀is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S or (C₆-C₁₀)aryl. In yet another embodiment, each R₁₀is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₁₀is 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R₁₀is (C₃-C₇)cycloalkyl. In yet another embodiment, each R₁₀is (C₆-C₁₀)aryl.

In some embodiments of the formulae above, each R₁₁is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, or —NH₂. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, or —CN. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, halogen, or —CN. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, halogen, or —CN. In yet another embodiment, each R₁₁is independently at each occurrence halogen, —OH, —CN, or —NH₂. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, or halogen. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, or halogen. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or halogen. In yet another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or —CN. In another embodiment, each R₁₁is independently at each occurrence (C₁-C₃)alkyl or (C₁-C₃)haloalkyl. In yet another embodiment, each R₁₁is independently at each occurrence halogen or —CN. In another embodiment, each Rn is independently at each occurrence (C₁-C₃)alkyl or halogen.

In some embodiments of the formulae above, each R₁₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, or —NH₂. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, or —CN. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, halogen, or —CN. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, halogen, or —CN. In yet another embodiment, each R₁₂is independently at each occurrence halogen, —OH, —CN, or —NH₂. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, or halogen. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, (C₁-C₆)alkoxy, or halogen. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or halogen. In yet another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, or —CN. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl or (C₁-C₃)haloalkyl. In yet another embodiment, each R₁₂is independently at each occurrence halogen or —CN. In another embodiment, each R₁₂is independently at each occurrence (C₁-C₃)alkyl or halogen.

In some embodiments of the formulae above, two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₆)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- or 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₆)cycloalkyl. In another embodiment, two R₁₂together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl.

In another embodiment, two R₁₂together with the atoms to which they are attached form a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₂together with the atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, R₁₃is selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₃is selected from (C₁-C₆)alkyl and (C₁-C₆)haloalkyl. In another embodiment, R₁₃is selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₃is selected from (C₃-C₇)cycloalkyl and 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R₁₃is selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S

In another embodiment, R₁₃is selected from (C₃-C₇)cycloalkyl and (C₆-C₁₀)aryl. In yet another embodiment, R₁₃is selected from 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₃is selected from (C₃-C₇)cycloalkyl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₁₃is selected from 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S and (C₆-C₁₀)aryl. In yet another embodiment, R₁₃is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₃is 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₃is (C₃-C₇)cycloalkyl. In yet another embodiment, each R₁₃is (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₁₄is selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₄is selected from (C₁-C₆)alkyl and (C₁-C₆)haloalkyl. In another embodiment, R₁₄is selected from (C₃-C₇)cycloalkyl, 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S, (C₆-C₁₀)aryl, and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₄is selected from (C₃-C₇)cycloalkyl and 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₁₄is selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S.

In another embodiment, R₁₄is selected from (C₃-C₇)cycloalkyl and (C₆-C₁₀)aryl. In yet another embodiment, R₁₄is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₄is selected from (C₃-C₇)cycloalkyl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R₁₄is selected from 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S and (C₆-C₁₀)aryl. In yet another embodiment, R₁₄is 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₄is 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁₄is (C₃-C₇)cycloalkyl. In yet another embodiment, R₁₄is (C₆-C₁₀)aryl.

In some embodiments of the formulae above, two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₆)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- or 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₆-C₇)cycloalkyl. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₆)cycloalkyl. In another embodiment, two R₁₅together with the atoms to which they are attached form a (C₄-C₅)cycloalkyl.

In another embodiment, two R₁₅together with the atoms to which they are attached form a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a 4- to 6-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R₁₅together with the atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S.

In some embodiments of the formulae above, m is 0, 1, or 2. In another embodiment, m is 0 or 1. In yet another embodiment, m is 1 or 2. In another embodiment, m is 0. In yet another embodiment, m is 1. In another embodiment, m is 2.

In some embodiments of the formulae above, m1 is 0, 1, or 2. In another embodiment, m1 is 0 or 1. In yet another embodiment, m1 is 1 or 2. In another embodiment, m1 is 0. In yet another embodiment, m1 is 1. In another embodiment, m1 is 2.

In some embodiments of the formulae above, n1 is 0, 1, or 2. In another embodiment, n1 is 1, 2, or 3. In another embodiment, n1 is 0 or 1. In another embodiment, n1 is 1 or 2. In another embodiment, n1 is 2 or 3. In another embodiment, n1 is 0. In another embodiment, n1 is 1. In another embodiment, n1 is 2. In another embodiment, n1 is 3.

In some embodiments of the formulae above, each s and n is independently 1, 2, or 3, wherein s+n is ≤4. In another embodiment, each s and n is independently 1 or 2, wherein s+n is ≤4. In another embodiment, each s and n is independently 2 or 3, wherein s+n is ≤4. In another embodiment, s is 1 and n is 1. In another embodiment, s is 2 and n is 2. In another embodiment, s is 1 and n is 2. In another embodiment, s is 2 and n is 1. In another embodiment, s is 3 and n is 1. In another embodiment, s is 1 and n is 3.

In some embodiments of the formulae above, R₁is

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and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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and n1 is 1 or 2.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, n1 is 1 or 2 and R₄is —OR₅.

In some embodiments of the formulae above, n1 is 1 or 2 and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, and m1 is 0.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, m1 is 0, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, m1 is 0, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, m1 is 0 and R₄is —NR₆R_6′.

In some embodiments of the formulae above, m1 is 0 and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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and m1 is 0.

In some embodiments of the formulae above, R₁is

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m1 is 0, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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m1 is 0, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, n1 is 1 or 2 and m1 is 0.

In some embodiments of the formulae above, n1 is 1 or 2, m1 is 0, and R₄is —OR₅.

In some embodiments of the formulae above, n1 is 1 or 2, m1 is 0, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, and m1 is 2.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, m1 is 2, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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n1 is 1 or 2, m1 is 2, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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m1 is 2.

In some embodiments of the formulae above, R₁is

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m1 is 2, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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m1 is 2, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, n1 is 1 or 2 and m1 is 2.

In some embodiments of the formulae above, n1 is 1 or 2, m1 is 2, and R₄is —OR₅.

In some embodiments of the formulae above, n1 is 1 or 2, m1 is 2, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, m1 is 2 and R₄is —OR₅.

In some embodiments of the formulae above, m1 is 2 and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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n is 2 and s is 1 or 2.

In some embodiments of the formulae above, R₁is

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and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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n is 2, s is 1 or 2, and m is 0 or 1.

In some embodiments of the formulae above, R₁is

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n is 2, s is 1 or 2, m is 0 or 1, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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n is 2, s is 1 or 2, m is 0 or 1, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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in is 2, s is 1 or 2, m is 0 or 1, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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n is 2, s is 1 or 2, m is 0 or 1, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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and m is 0 or 1.

In some embodiments of the formulae above, R₁is

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m is 0 or 1, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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m is 0 or 1, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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m is 0 or 1, and R₄is —OR₅.

In some embodiments of the formulae above, R₁is

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m is 0 or 1, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, n is 2, s is 1 or 2, and m is 0 or 1.

In some embodiments of the formulae above, n is 2, s is 1 or 2, m is 0 or 1, and R₄is —OR₅.

In some embodiments of the formulae above, n is 2, s is 1 or 2, m is 0 or 1, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, n is 2, s is 1 or 2 and R₄is —OR₅.

In some embodiments of the formulae above, n is 2, s is 1 or 2 and R₄is —NR₆R_6′.

In some embodiments of the formulae above, m is 0 or 1, and R₄is —OR₅.

In some embodiments of the formulae above, m is 0 or 1, and R₄is —NR₆R_6′.

In some embodiments of the formulae above, R₁is

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m1 is 0, R₄is —OR₅, and R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three substituents each independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, and R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl.

In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three substituents each independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, and n1 is 0, 1, or 2. In another embodiment, R₁is

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In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 0, 1, or 2. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 0. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 1. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 2.

In some embodiments of the formulae above, R₁is

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m1 is 0, R₄is —OR₅, and R₅is H or (C₁-C₆)alkyl optionally substituted with one to three substituents each independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, and R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl.

In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H or (C₁-C₆)alkyl optionally substituted with one to three substituents each independently selected from (C₆-C₁₀)aryl and 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from O, N, and S, and n1 is 0, 1, or 2. In another embodiment, R₁is

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In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 0, 1, or 2. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 0. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 1. In another embodiment, R₁is

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m1 is 0, R₄is —OR₅, R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl, and n1 is 2.

In some embodiments of the formulae above, R₁is

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m1 is 0, R₄is —NR₆R_6′, and R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, and n1 is 0, 1, or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, and n1 is 2.

In some embodiments of the formulae above, R₁is

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m1 is 0, R₄is —NR₆R_6′, and R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, and R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 0, 1, or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 0.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 1. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 2.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 0, 1, or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 0.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 1. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 2.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, and R₇is (C₆-C₁₀)aryl.

In another embodiment, R₁is

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In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl, and n1 is 1 or 2. In another embodiment, R₁is

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In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆and R_6′ are each independently H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl, wherein the alkyl is optionally substituted with one to three R₇; or R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈, R₇is (C₆-C₁₀)aryl, and n1 is 1. In another embodiment, R₁is

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In some embodiments of the formulae above, R₁is

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m1 is 0, R₄is —NR₆R_6′, and R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 0, 1, or 2.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 0.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 1. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 2.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 0, 1, or 2.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 0.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 1. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 2.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H, (C₁-C₆)haloalkyl, or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl, and n1 is 1. In another embodiment, R₁is

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In some embodiments of the formulae above, R₁is

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m1 is 0, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉, and n1 is 1 or 2. In another embodiment, R₁is

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In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉.

In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 1 or 2. In another embodiment, R₁is

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m1 is 0, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₇is (C₆-C₁₀)aryl optionally substituted with one or two R₉, and n1 is 1. In another embodiment, R₁is

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In another embodiment, R₁is

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In some embodiments of the formulae above, R₁is

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m is 0, n is 1, and s is 1. In another embodiment, R₁is

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m is 0, n is 1, s is 1, and R₄is —OR₅. In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —OR₅, and R₅is H, (C₆-C₁₀)aryl, or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl. In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —OR₅, and R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₁is

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m is 0, n is 1, s is 1, and R₄is —NR₆R_6′. In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —NR₆R_6′, and R₆is H or C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl optionally substituted with one or more R₉.

In another embodiment, R₁is

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m is 0, n is 1, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₁is

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m is 0, n is 2, and s is 1. In another embodiment, R₁is

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m is 0, n is 2, s is 1, and R₄is —OR₅. In another embodiment, R₁is

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m is 0, n is 2, s is 1, R₄is —OR₅, and R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₁is

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m is 0, n is 2, s is 1, and R₄is —NR₆R_6′. In another embodiment, R₁is

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m is 0, n is 2, s is 1, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 2, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 2, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m is 0, n is 2, s is 1, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl optionally substituted with one or more R₉.

In another embodiment, R₁is

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In some embodiments of the formulae above, R₁is

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m is 0, n is 2, and s is 2. In another embodiment, R₁is

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n is 2, s is 2, and R₄is —OR₅. In another embodiment, R₁is

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m is 0, n is 2, s is 2, R₄is —OR₅, and R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₁is

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m is 0, n is 2, s is 2, and R₄is —NR₆R_6′. In another embodiment, R₁is

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m is 0, n is 2, s is 2, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 2, s is 2, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 2, s is 2, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m is 0, n is 2, s is 2, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl optionally substituted with one or more R₉.

In another embodiment, R₁is

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In some embodiments of the formulae above, R₁is

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m is 0, n is 2, s is 1 or 2, and R₄is —OR₅. In another embodiment, R₁is

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m is 0, n is 2, s is 1 or 2, R₄is —OR₅and R₅is H or (C₁-C₆)alkyl optionally substituted with one to three (C₆-C₁₀)aryl.

In some embodiments of the formulae above, R₁is

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m is 0, n is 2, s is 1 or 2, and R₄is —NR₆R_6′. In another embodiment, R₁is

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m is 0, n is 2, s is 1 or 2, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 2, s is 1 or 2, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇. In another embodiment, R₁is

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m is 0, n is 2, s is 1 or 2, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₃-C₇)cycloalkyl or (C₆-C₁₀)aryl, wherein the cycloalkyl and aryl are optionally substituted with one or two R₉.

In another embodiment, R₁is

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m is 0, n is 2, s is 1 or 2, R₄is —NR₆R_6′, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, and R₇is (C₆-C₁₀)aryl optionally substituted with one or more R₉.

In another embodiment, R₁is

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In another embodiment, R₁is

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m1 is 0, n1 is 1, 2, or 3, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In another embodiment, R₁is

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m1 is 0, n1 is 2 or 3, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, or R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 1 or 2, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 1, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 2, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 3, R₄is —NR₆R_6′, and R₆is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, R_6′ is H or (C₁-C₆)alkyl optionally substituted with one to three R₇, or R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 1, 2, or 3, R₄is —NR₆R_6′, and R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In yet another embodiment, R₁is

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m1 is 0, n1 is 2 or 3, R₄is —NR₆R_6′, and R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 1 or 2, R₄is —NR₆R_6′, and R₆and R_6′together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In yet another embodiment, R₁is

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m1 is 0, n1 is 1, R₄is —NR₆R_6′, and R₆and R_6′, together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

In another embodiment, R₁is

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m1 is 0, n1 is 2, R₄is —NR₆R_6′, and R₆and R_6′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈. In yet another embodiment, R₁is

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m1 is 0, n1 is 3, R₄is —NR₆R_6′, and R₆and R_6′, together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally comprising 1-2 additional heteroatoms selected from O, N, and S, and optionally substituted with one to four R₈.

Embodiment 1: A compound of Formula (I′), wherein:

X₁and X₂are each independently H, (C₁-C₄)alkyl, (C₁-C₆)alkoxy, (C₁-C₄)haloalkyl, (C₁-C₆)haloalkoxy, (C₃-C₇)cycloalkyl, halogen, —CN, —OH, or —NH₂;

R_xis H or D;

R₁is

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each R₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —CN, —OH, or —NH₂; or

two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S; or

each R₃is (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —OH, or —NH₂;

R₄is —OR₅or —NR₆R_6′;

each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, or —NH₂; or two R₉together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 5- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S optionally substituted with one or more substituents each independently selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, and —NH₂; or two R₉when on adjacent atoms together with the atoms to which they are attached form a (C₆-C₁₀)aryl, or 5- or 6-membered heteroaryl comprising 1-3 heteroatoms selected from 0, N, and S;

each R₁₁is independently at each occurrence selected from (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, and —NH₂;

each R₁₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkoxy, halogen, —OH, —CN, or —NH₂;

two R₁₂together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

two R₁₅together with the atoms to which they are attached form a (C₄-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

m and m1 are each independently 0, 1 or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≤4;

or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

Embodiment 2. The compound of Embodiment 1, having a Formula (I), wherein:

R_xis H or D;

R₁is

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each R₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —CN, —OH, or —NH₂; or

two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S; or

each R₃is (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, OH, or —NH₂;

R₄is —OR₅or —NR₆R_6′;

two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂; or

m and m1 are each independently 0, 1, or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≤4;

or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

Embodiment 2A. The compound of Embodiment 1, having a Formula (I), wherein:

R_xis H or D;

R₁is

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each R₂is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —CN, —OH, or —NH₂; or

two R₂together with the carbon atoms to which they are attached form a (C₃-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-3 heteroatoms selected from O, N, and S; or two R₂together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring comprising 1-3 heteroatoms selected from O, N, and S; or

each R₃is (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)haloalkyl, (C₁-C₆)haloalkoxy, halogen, —OH, or —NH₂;

R₄is —OR₅or —NR₆R_6′;

each R₈is independently at each occurrence halogen, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —CN, —OH, or —NH₂; or

two R₈together with the atoms to which they are attached form a (C₅-C₇)cycloalkyl or a 4- to 7-membered heterocycloalkyl ring comprising 1-2 heteroatoms selected from O, N, and S;

each R₉is independently at each occurrence (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, halogen, —OH, —CN, or —NH₂; or

m and m1 are each independently 0, 1 or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≤4;

or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

Embodiment 3. The compound of any one of Embodiments 1, 2, and 2A, wherein R₁is

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Embodiment 4. The compound of any one of Embodiments 1, 2, and 2A, wherein n1 is 0, 1, or 2.

Embodiment 5. The compound of any one of Embodiments 1 to 3 and 2A, wherein m1 is 0.

Embodiment 6. The compound of any one of Embodiments 1 to 3 and 2A, wherein m1 is 2.

Embodiment 7. The compound of any one of Embodiments 1, 2, and 2A, wherein R₁is

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Embodiment 8. The compound of Embodiment 7, wherein n is 2 and s is 1 or 2.

Embodiment 9. The compound of Embodiment 7 or 8, wherein m is 0 or 1.

Embodiment 10. The compound of any one of Embodiments 1, 2, and 2A, having a Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

Embodiment 11. The compound of any one of Embodiments 1, 2, and 2A, having a Formula (Ic), Formula (Id), Formula (Ie), Formula (If), Formula (Ig), Formula (Ih), Formula (Ii), or Formula (Ij), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

Embodiment 12. The compound of any one of Embodiments 1, 2, and 2A, having a Formula (Ik), Formula (II), Formula (Im), Formula (In), Formula (To), or Formula (Ip), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

Embodiment 13. The compound of any one of Embodiments 1 to 12 and 2A, wherein R₄is —OR₅.

Embodiment 14. The compound of any one of Embodiments 1 to 12 and 2A, wherein R₄is —NR₆R_6′.

Embodiment 15. The compound of any one of Embodiments 1, 2, and 2A, having a Formula (Iq), Formula (Ir), Formula (Is), or Formula (It), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

Embodiment 16. The compound of Embodiment 1 selected from:

Compound Structure/Compound Name

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3-(5-(((1S,2S)-2-((2,2-

difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((2,2-

difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((2,2-

difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((2,2-

difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((2,2-

difluoroethyl)(ethyl)ammino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione

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3-(5-(((1S,2R)-2-(benzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(benzylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(benzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(benzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(benzylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1-methyloctahydrocyclopenta[b]pyrrol-6-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-methoxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-methoxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-methoxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-methoxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-methoxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-hydroxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-hydroxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-hydroxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-hydroxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-hydroxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-hydroxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-hydroxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-hydroxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-hydroxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-hydroxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(isobutylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(isobutylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(isobutylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(isobutylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(isobutylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4,4-difluoropiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4,4-difluoropiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4,4-difluoropiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4,4-difluoropiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(benzyloxy)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(benzyloxy)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(benzyloxy)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(benzyloxy)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(benzyloxy)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diethylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(diethylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(diethylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(diethylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(diethylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(((1-

(trifluoromethyl)cyclopropyl)methyl)amino)

cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-(((1-

(trifluoromethyl)cyclopropyl)methyl)amino)

cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-(((1-

(trifluoromethyl)cyclopropyl)methyl)amino)

cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-(((1-

(trifluoromethyl)cyclopropyl)methyl)amino)

cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-((1-(((1-

(trifluoromethyl)cyclopropyl)methyl)amino)

cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-aminocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-aminocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-aminocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-aminocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-aminocyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(diethylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diethylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(diethylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(diethylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(diethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-aminocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-aminocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-aminocyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-aminocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-aminocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-azabicyclo[3.2.1]octan-3-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-azabicyclo[3.2.1]octan-3-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-azabicyclo[3.2.1]octan-3-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-azabicyclo[3.2.1]octan-3-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-azabicyclo[3.2.1]octan-3-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(1,4-dioxa-8-azaspiro[4.5]decan-

8-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(1,4-dioxa-8-azaspiro[4.5]decan-

8-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(1,4-dioxa-8-azaspiro[4.5]decan-

8-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(1,4-dioxa-8-azaspiro[4.5]decan-

8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(1,4-dioxa-8-azaspiro[4.5]decan-8-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(8-oxa-3-azabicyclo[3.2.1]octan-

3-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(8-oxa-3-azabicyclo[3.2.1]octan-

3-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(8-oxa-3-azabicyclo[3.2.1]octan-

3-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(8-oxa-3-azabicyclo[3.2.1]octan-

3-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(8-oxa-3-azabicyclo[3.2.1]octan-3-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-

phenoxycyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-

phenoxycyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-

phenoxycyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-

phenoxycyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-

phenoxycyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(benzylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(benzylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(benzylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(benzylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(benzylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4S)-3-(benzylamino)tetrahydro-2H-

pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-

2,6-dione;

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3-(5-(((3R,4S)-3-(benzylamino)tetrahydro-2H-

pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-

2,6-dione;

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3-(5-(((3R,4R)-3-(benzylamino)tetrahydro-2H-

pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-

2,6-dione;

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3-(5-(((3S,4R)-3-(benzylamino)tetrahydro-2H-

pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-

2,6-dione;

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3-(5-((3-(benzylamino)tetrahydro-2H-pyran-4-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(benzylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(benzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(benzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(benzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(benzylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(((R)-1-

phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-(((R)-1-

phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-(((R)-1-

phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-(((R)-1-

phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-(((R)-1-

phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethyl(2-

fluoroethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethyl(2-

fluoroethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethyl(2-

fluoroethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethyl(2-

fluoroethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(2-

fluoroethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-

(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(isopropyl)amino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-methoxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-methoxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-methoxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-methoxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-methoxycyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-hydroxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-hydroxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-hydroxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-hydroxycyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-hydroxycyclohexyl)oxy)-1-oxoisoindolin-

2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-

(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-

(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(piperidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-(piperidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-(piperidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-(piperidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-(piperidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(5-(((1S,2S)-2-morpholinocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-morpholinocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-morpholinocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-morpholinocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-morpholinocyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(dibenzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(dibenzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(dibenzylamino)cyclohexyl)oxy)-1-oxoisoindolin-

2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(dibenzylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(dibenzylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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cis-3-(5-((2-(diethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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trans-3-(5-((2-(diethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(methylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(methylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(methylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(methylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(methylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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1-((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

methylpiperidine-4-carbonitrile;

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1-((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

methylpiperidine-4-carbonitrile;

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1-((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

methylpiperidine-4-carbonitrile;

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1-((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

methylpiperidine-4-carbonitrile;

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1-(2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

methylpiperidine-4-carbonitrile;

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3-(5-(((1S,2S)-2-

(benzyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(benzyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(benzyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(benzyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(benzyl(methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4S)-3-aminotetrahydro-2H-pyran-4-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3R,4S)-3-aminotetrahydro-2H-pyran-4-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3R,4R)-3-aminotetrahydro-2H-pyran-4-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4R)-3-aminotetrahydro-2H-pyran-4-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((3-aminotetrahydro-2H-pyran-4-yl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1S,2S)-2-(benzylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1R,2R)-2-(benzylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1S,2R)-2-(benzylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1R,2S)-2-(benzylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(2-(benzylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3R,4S)-4-aminotetrahydrofuran-3-yl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3R,4R)-4-aminotetrahydrofuran-3-yl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4R)-4-aminotetrahydrofuran-3-yl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4S)-4-aminotetrahydrofuran-3-yl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((4-aminotetrahydrofuran-3-yl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3R,4S)-4-(diethylamino)tetrahydrofuran-3-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3R,4R)-4-(diethylamino)tetrahydrofuran-3-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4R)-4-(diethylamino)tetrahydrofuran-3-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((3S,4S)-4-(diethylamino)tetrahydrofuran-3-

yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((4-(diethylamino)tetrahydrofuran-3-yl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-(5-((1S,2S)-2-(diethylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1R,2S)-2-(diethylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1R,2R)-2-(diethylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((1S,2R)-2-(diethylamino)cycobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(2-(diethylamino)cyclobutoxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethyl((3-

fluorobicyclo[1.1.1]pentan-1-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethyl((3-

fluorobicyco[1.1.]pentan-1-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethyl((3-

fluorobicyclo[1.1.1]pentan-1-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethyl((3-

fluorobicyclo[1.1.1]pentan-1-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl((3-fluorobicyclo[1.1.1]pentan-1-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-(5-(((1S,2S)-2-

(isopropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(isopropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(isopropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(isopropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(isopropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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2-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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2-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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2-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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2-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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2-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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3-(5-(((1S,2S)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3-fluorobicyclo[1.1.1]pentan-1-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-hydroxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-hydroxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-hydroxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-hydroxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-hydroxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-hydroxy-4-

(trifluoromethy)piperidin-1-yl)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-hydroxy-4-

(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-hydroxy-4-

(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-hydroxy-4-

(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-hydroxy-4-(trifluoromethyl)piperidin-

1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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1-((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

(trifluoromethyl)piperidine-4-carbonitrile;

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1-((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

(trifluoromethyl)piperidine-4-carbonitrile;

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1-((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

(trifluoromethyl)piperidine-4-carbonitrile;

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1-((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

(trifluoromethyl)piperidine-4-carbonitrile;

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1-(2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-yl)oxy)cyclopentyl)-4-

(trifluoromethyl)piperidine-4-carbonitrile;

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3-(5-(((1S,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopenty)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-(3-(2,2,2-trifluoroethoxy)azetidin-

1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-

2,6-dione;

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3-(5-(((1S,2S)-2-(3-(2,2,2-difluoroethoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-oxoisindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(2,2-difluoroethoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(2,2-difluoroethoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(2,2-difluoroethoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(2,2-difluoroethoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(cyclopropylmethoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-

(cyclopropylmethoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-

(cyclopropylmethoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-

(cyclopropylmethoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(cyclopropylmethoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(benzyloxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(benzyloxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(benzyloxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(benzyloxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(benzyloxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-isopropoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-isopropoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-isopropoxyazetidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-isopropoxyazetidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(3-isopropoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-ethoxyazetidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-ethoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-ethoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-ethoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-ethoxyazetidin-1-yl)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(benzyloxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(benzyloxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(benzyloxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(benzyloxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(benzyloxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-ethoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-ethoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-ethoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-ethoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-ethoxyazetidin-1-yl)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(3,3-

difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(3,3-

difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(3,3-

difluorocyclobutoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(3,3-

difluorocyclobutoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(3,3-difluorocyclobutoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-hydroxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-hydroxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-hydroxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-hydroxypiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(4-hydroxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(4-oxopiperidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(5-(((1S,2S)-2-(3-hydroxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-hydroxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-hydroxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-hydroxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-hydroxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione

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3-(5-(((1S,2S)-2-(3-hydroxy-3-methylazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-hydroxy-3-methylazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-hydroxy-3-methylazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-hydroxy-3-methylazetidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(3-hydroxy-3-methylazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(isobutylamino)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(isobutylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(isobutylamino)cyclopenty)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(isobutylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(isobutylamino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-

(ethyl(methyl)amino)cyclopentyl)oxy)-1-

oxoisoindoin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(ethyl(methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(ethyl(methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(ethyl(methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((3aR,6aS)-tetrahydro-1H-

furo[3,4-c]pyrrol-5(3H)-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-((3aR,6aS)-tetrahydro-1H-

furo[3,4-c]pyrrol-5(3H)-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-((3aR,6aS)-tetrahydro-1H-

furo[3,4-c]pyrrol-5(3H)-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-((3aR,6aS)-tetrahydro-1H-

furo[3,4-c]pyrrol-5(3H)-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-((3aR,6aS)-tetrahydro-1H-furo[3,4-

c]pyrrol-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-(tetrahydro-1H-furo[3,4-c]pyrrol-

5(3H)-yl)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyridin-2-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyridin-2-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyridin-2-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyridin-2-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyridin-2-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(pyrrolidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-(pyrrolidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-(pyrrolidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-(pyrrolidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-(pyrrolidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(5-(((1S,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclopentyl)oxy)-1-oxoisoindoline-2-

yl)piperidine-2,6-dione

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3-(5-(((1R,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(bis(3-methyloxetan-3-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(bis(3-methyloxetan-3-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(bis((3-methyloxetan-3-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(bis((3-methyloxetan-3-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(bis((3-methyloxetan-3-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyridin-3-

ylmethy)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyridin-3-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyridin-3-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione

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3-(1-oxo-5-(((1R,2S)-2-((pyridin-3-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyridin-3-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione

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3-(1-oxo-5-(((1S,2S)-2-((pyridin-4-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyridin-4-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyridin-4-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyridin-4-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyridin-4-

ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-methoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4,4-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4,4-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4,4-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4,4-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(4,4-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-methoxypiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-methoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-methoxypiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-methoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-methoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethyl(oxetan-3-

ylmethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethyl(oxetan-3-

ylmethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethyl(oxetan-3-

ylmethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethyl(oxetan-3-

ylmethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(oxetan-3-

ylmethyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(isoindolin-2-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(isoindolin-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(isoindolin-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(isoindolin-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(isoindolin-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-methoxyazetidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-methoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-methoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-methoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-methoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-ethoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-ethoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-ethoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-ethoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-ethoxy-4-methylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1R,4S)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1R,4R)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1R,4R)-4-

methoxycyclohexy)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1R,4S)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((((1R,4R)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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(1S,4R)-4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-

carbonitrile;

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(1R,4r)-4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-

carbonitrile;

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(1R,4r)-4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-

carbonitrile;

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(1S,4r)-4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-

carbonitrile;

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(1r,4r)-4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-

carbonitrile;

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4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-

carbonitrile;

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3-(5-(((1S,2S)-2-(((4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1S,3R)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1R,3S)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclopenta)(ethyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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trans-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-

1-oxoisoindolin-5-

yl)oxy)cyclopenty)(ethyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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cis-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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3-(5-(((1S,2S)-2-(4-fluoropiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-fluoropiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-fluoropiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-fluoropiperidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(4-fluoropiperidin-1-yl)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(1,5-oxazocan-5-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(1,5-oxazocan-5-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(1,5-oxazocan-5-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(1,5-oxazocan-5-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(1,5-oxazocan-5-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3,3-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3,3-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3,3-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3,3-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3,3-dimethylpiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethyl(((1R,4S)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1R,4S)-4-

methoxycyclohexyl)methyl)(methyl)amino)

cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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trans-3-(5-((2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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cis-3-(5-((2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((4,4-

difluorocyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((4,4-

difluorocyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((4,4-

difluorocyclohexyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((4,4-

difluorocyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((4,4-

difluorocyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((1H-indol-5-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((1H-indol-5-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((1H-indol-5-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((1H-indol-5-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((1H-indol-5-

yl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-(tert-butoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-(tert-butoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-(tert-butoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-(tert-butoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-(tert-butoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-8-azaspiro[4.5]decan-8-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-8-azaspiro[4.5]decan-8-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(2-oxa-8-azaspiro[4.5]decan-8-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-8-azaspiro[4.5]decan-8-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(2-oxa-8-azaspiro[4.5]decan-8-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(2-methoxyphenoxy)azetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(6-azaspiro[3.4]nonan-6-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(6-azaspiro[3.5]nonan-6-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((((1R,2R)-2-(6-azaspiro[3.5]nonan-6-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(6-azaspiro[3.5]nonan-6-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(6-azaspiro[3.5]nonan-6-

yl)cyclopenty)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethyl(((1S,3R)-3-

methoxycyclobutyl)methyl)amino)cyclopenty)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethyl(((1s,3S)-3-

methoxycyclobutyl)methyl)amino)cyclopenty)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethyl(((1s,3S)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethyl(((1s,3R)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(((1s,3s)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(diethylamino)-4,4-

dimethylcyclopenty)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(diethylamino)-4,4-

dimethylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethyl(((1R,3S)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethyl(((1r,3R)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethyl(((1r,3R)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethyl(((1r,3S)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(((1r,3r)-3-

methoxycyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(8-oxa-2-azaspiro[4.5]decan-2-

yl)cyclopenty)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(8-oxa-2-azaspiro[4.5]decan-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(8-oxa-2-azaspiro[4.5]decan-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(8-oxa-2-azaspiro[4.5]decan-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(8-oxa-2-azaspiro[4.5]decan-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-

thiomorpholinocyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-

thiomorpholinocyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-

thiomorpholinocyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-

thiomorpholinocyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-

thiomorpholinocyclopentyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(1,4-oxazepan-4-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(1,4-oxazepan-4-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(1,4-oxazepan-4-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(1,4-oxazepan-4-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(1,4-oxazepan-4-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-isopropoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-isopropoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-isopropoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-isopropoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-isopropoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-

(cyclopropylmethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-

(cyclopropylmethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-

(cyclopropylmethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-

(cyclopropylmethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-(cyclopropylmethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((3aR,4R,7S,7aS)-octahydro-2H-

4,7-epoxyisoindol-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((3aR,4R,7S,7aS)-octahydro-2H-

4,7-epoxyisoindol-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((3aR,4R,7S,7aS)-octahydro-2H-

4,7-epoxyisoindol-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((3aR,4R,7S,7aS)-octahydro-2H-

4,7-epoxyisoindol-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((3aR,4R,7S,7aS)-octahydro-2H-4,7-

epoxyisoindol-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-ethoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-ethoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-ethoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-ethoxypiperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-ethoxypiperidin-1-yl)cyclopentyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(7,8-dihydro-1,6-naphthyridin-

6(5H)-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(7,8-dihydro-1,6-naphthyridin-

6(5H)-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(7,8-dihydro-1,6-naphthyridin-

6(5H)-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(7,8-dihydro-1,6-naphthyridin-

6(5H)-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(7,8-dihydro-1,6-naphthyridin-6(5H)-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1S,4R)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1s,4S)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1s,4S)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1s,4R)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((((1s,4s)-4-

methoxycyclohexyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((R)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((R)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((R)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((R)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-((R)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((S)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((S)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((S)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((S)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((S)-3-methoxypyrrolidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclopentyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-(difluoromethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-(difluoromethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-(difluoromethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-(difluoromethoxy)piperidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-difluoromethoxy)piperidin-1-

y)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(1,3-dihydro-2H-pyrrolo[3,4-

c]pyridin-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(1,3-dihydro-2H-pyrrolo[3,4-

c]pyridin-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(1,3-dihydro-2H-pyrrolo[3,4-

c]pyridin-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(1,3-dihydro-2H-pyrrolo[3,4-

c]pyridin-2-yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-

(propylamino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-

(propylamino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-

(propylamino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-

(propylamino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-

(propylamino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(dipropylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diipropylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(dipropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(dipropylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(dipropylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyridin-4-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyridin-4-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyridin-4-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyridin-4-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyridin-3-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyridin-3-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyridin-3-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyridin-3-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyridin-3-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((1-ethyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((1-ethyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((1-ethyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((1-ethyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((1-ethyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((1-isopropyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((1-isopropyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((1-isopropyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((1-isopropyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((1-isopropyl-1H-pyrazol-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-

(ethyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(ethyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(ethyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(ethyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethyl(methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(dimethylamino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(dimethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(dimethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(dimethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(dimethylamino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((oxetan-3-

ylmethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((oxetan-3-

ylmethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((oxetan-3-

ylmethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((oxetan-3-

ylmethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((oxetan-3-

ylmethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((2-

hydroxyethy)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((2-

hydroxyethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((2-

hydroxyethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((2-

hydroxyethyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((2-hydroxyethyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(pyrrolidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-(pyrrolidin-1-

yl)cyclohexyl)oxy)isoindoin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-(pyrrolidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-(pyrrolidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-(pyrrolidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(5-(((1S,2S)-2-morpholinocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-morpholinocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-morpholinocyclohexy)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-morpholinocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-morpholinocyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyridin-2-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyridin-2-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyridin-2-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyridin-2-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyridin-2-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((3-hydroxy-3-

methylbutyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((3-hydroxy-3-

methylbutyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((3-hydroxy-3-

methylbutyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((3-hydroxy-3-

methylbutyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((3-hydroxy-3-

methylbutyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3-methyloxetan-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3-methyloxetan-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3-methyloxetan-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3-methyloxetan-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3-methyloxetan-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-methoxy-4-methylpyridin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-methoxy-4-methylpiperidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(4-methoxy-4-methylpiperidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-methoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-methoxyazetidin)-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-methoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-methoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-methoxyazetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((6-methylpyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((6-methylpyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((6-methylpyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((6-methylpyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((6-methylpyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((5-methoxypyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((5-methoxpyridin-2-

yl)methyl)amino)cyclohexy)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((5-methoxypyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((5-methoxpyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((5-methoxypyridin-2-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((6-methoxypyridin-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((6-methoxypyridin-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((6-methoxypyridin-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((6-methoxypyridin-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((6-methoxypyridin-3-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((2-hydroxy-2-

methylpropyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((2-hydroxy-2-

methylpropyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((2-hydroxy-2-

methylpropyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((2-hydroxy-2-

methylpropyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((2-hydroxy-2-

methylpropyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-1-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1S,3R)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1R,3R)-3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1R,3R)-3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1S,3r)-3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl-1-

methylcyclobutane-1-carbonitrile;

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(1r,3r)-3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbontrile;

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(1R,3S)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1S,3s)-3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1S,3s)-3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1R,3s)-3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-

yl)-1-oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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(1s,3s)-3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)-1-

methylcyclobutane-1-carbonitrile;

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3-(oxo-5-(((1S,2S)-2-(piperidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-(piperidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-(piperidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-(piperidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-(piperidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2S)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3-

methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1S,3R)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1s,3S)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1s,3S)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1s,3R)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((((1s,3s)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((cis-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((cis-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((cis-3-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((cis-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((cis-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1R,3S)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1s,3S)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1s,3S)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1s,3R)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((1s,3s)-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((trans-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((trans-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((trans-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((trans-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((trans-3-

methoxycyclobutyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1r,4S)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1r,4R)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1r,4R)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1r,4S)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((((1r,4r)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((4-methyltetrahydro-2H-pyran-

4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((4-methyltetrahydro-2H-pyran-

4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((4-methyltetrahydro-2H-pyran-

4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((4-methyltetrahydro-2H-pyran-

4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((4-methyltetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyrimidin-5-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyrimidin-5-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyrimidin-5-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyrimidin-5-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyrimidin-5-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((2-(tetrahydro-2H-pyran-

4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((2-(tetrahydro-2H-pyran-

4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((2-tetrahydro-2H-pyran-

4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((2-(tetrahydro-2H-pyran-

4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((2-(tetrahydro-2H-pyran-4-

yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-7-azaspiro[3.5]nonan-7-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((4-methoxytetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((4-methoxytetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((4-methoxytetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((4-methoxytetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((4-methoxytetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((2,2-dimethyltetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((2,2-dimethyltetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((2,2-dimethyltetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((2,2-dimethyltetrahydro-2H-

pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((2,2-dimethyltetrahydro-2H-pyran-4-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((7-oxaspiro[3.5]nonan-2-

yl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((7-oxaspiro[3.5]nonan-2-

yl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((7-oxaspiro[3.5]nonan-2-

yl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((7-oxaspiro[3.5]nonan-2-

yl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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1-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-

carbonitrile;

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1-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-

carbonitrile;

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1-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-

carbonitrile;

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1-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-

carbonitrile;

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1-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-

carbonitrile;

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3-(5-(((1S,2S)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(2-chlorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(2-methoxyphenoxy)azetidin-

1-yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(2-methoxyphenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-((pyrazolo[1,5-

a]pyrimidin-6-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-((pyrazolo[1,5-

a]pyrimidin-6-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-((pyrazolo[1,5-

a]pyrimidin-6-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-((pyrazolo[1,5-

a]pyrimidin-6-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-((pyrazolo[1,5-a]pyrimidin-6-

ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((4,4-

difluorocyclohexyl)amino)cyclohexyl)amino)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((4,4-

difluorocyclohexyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((4,4-

difluorocyclohexyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((4,4-

difluorocyclohexyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((4,4-

difluorocyclohexyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((2,4-

difluorobenzyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((2,4-

difluorobenzyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((2,4-

difluorobenzyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((2,4-

difluorobenzyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((2,4-

difluorobenzyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((1R,2R)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((1R,2R)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((1R,2R)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((1R,2R)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((1R,2R)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((1S,2S)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((1S,2S)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((1S,2S)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((1S,2S)-2-

methoxycyclopentyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)bicyclo[1.1.1]

pentane-1-carbonitrile;

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3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)bicyclo[1.1.1]

pentane-1-carbonitrile;

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3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)bicyclo[1.1.1]

pentane-1-carbonitrile;

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3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)bicyclo[1.1.1]

pentane-1-carbonitrile;

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3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)bicyclo[1.1.1]

pentane-1-carbonitrile;

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3-(5-(((1S,2S)-2-(3-(3-fluorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-(3-fluorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-(3-fluorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-(3-fluorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-(3-fluorophenoxy)azetidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3,3-

difluorocyclobuyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3,3-

difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1S,4R)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1s,4S)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1s,4S)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1s,4R)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((1s,4s)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((cis-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((trans-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(bis(((1R,4S)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(bis(((1r,4R)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(bis(((1r,4S)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(bis(((1r,4R)-4-

methoxycyclohexyl)methyl)amino)cyclohexyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)amino)methyl)benzonitrile;

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4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)(methyl)amino)methyl)

benzonitrile;

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4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)(methyl)amino)methyl)

benzonitrile;

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4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)(methyl)amino)methyl)

benzonitrile;

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4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)(methyl)amino)methyl)

benzonitrile;

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4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-

oxoisoindolin-5-

yl)oxy)cyclohexyl)(methyl)amino)methyl)

benzonitrile;

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3-(5-(((1S,2S)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3-fluorobicyclo[1.1.1]pentan-1-

yl)methyl)amino)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3,3-difluoropyrrolidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3,3-difluoropyrrolidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3,3-difluoropyrrolidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3,3-difluoropyrrolidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3,3-difluoropyrrolidin-1-

yl)cyclohexyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(ethylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(ethylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(ethylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(ethylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(ethylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(benzylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(benzylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(benzylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(benzylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(benzylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(diethylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diethylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(diethylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(diethylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(diethylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(4-methoxy-4-methylpiperidin-1-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(4-methoxy-4-methylpiperidin-1-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(4-methoxy-4-methylpiperidin-1-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(4-methoxy-4-methylpiperidin-1-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-((2-(4-methoxy-4-methylpiperidin-1-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(isobutylamino)cycloheptyl)oxy)-

1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-

(isobutylamino)cycloheptyl)oxy-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-

(isobutylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-

(isobutylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(isobutylamino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-

(propylamino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-

(propylamino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-

(propylamino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione

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3-(1-oxo-5-(((1R,2S)-2-

(propylamino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-

(propylamino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-((((1R,4S)-4-

methoxycyclohexyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-((((1r,4R)-4-

methoxycyclohexyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-((((1r,4R)-4-

methoxycyclohexyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-((((1r,4S)-4-

methoxycyclohexyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-((((1r,4r)-4-

methoxycyclohexyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-(((tetrahydro-2H-pyran-4-

yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3-methyloxetan-3-

yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3-methyloxetan-3-

yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3-methyloxetan-3-

yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3-methyloxetan-3-

yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3-methyloxetan-3-

yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3-fluorobicyclo[1.1.1]pentan-

1-yl)methyl)amino)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino)

cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(3-methoxyazetidin-1-

yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-methoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-methoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-methoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-methoxyazetidin-1-

yl)cycloheptyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(((3,3-

difluorocyclobutyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(((3,3-

difluorocyclobutyl)methyl)amino)cycloheptyl)

oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(diethylamino)-3-

methylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2S)-2-(diethylamino)-3-

methylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(diethylamino)-3-

methylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(diethylamino)-3-

methylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(diethylamino)-3-

methylcyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(3-(pyridazin-3-

yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2R)-2-(3-(pyridazin-3-

yloxy)azetdin-1-yl)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2R)-2-(3-(pyridazin-3-

yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1R,2S)-2-(3-(pyridazin-3-

yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-

yl)piperidine-2,6-dione;

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3-(1-oxo-5-((2-(3-(pyridazin-3-yloxy)azetidin-1-

yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(5-(((1S,2S)-2-(3-isopropoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1S,2R)-2-(3-isopropoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2R)-2-(3-isopropoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-(((1R,2S)-2-(3-isopropoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(5-((2-(3-isopropoxyazetidin-1-

yl)cyclopentyl)oxy)-1-

oxoisoindolin-2-yl)piperidine-2,6-dione;

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3-(1-oxo-5-(((1S,2S)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1S,2R)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2R)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-(((1R,2S)-2-(3-(2,2,2-

trifluoroethoxy)azetidin-1-

yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-

dione;

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3-(1-oxo-5-((2-(3-(2,2,2-trifluoroethoxy)azetidin-

1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-

2,6-dione;

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