3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and their use in the treatment of Ikaros family zinc finger 2 (IKZF2) dependent diseases

Abstract

The present disclosure provides a compound of formula (I') [Formula 1] or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein R x , X1, X2, and R1 are as defined herein), and their use in the treatment of Ikaros family zinc finger 2 (IKZF2)-dependent diseases.

Description

[Technical field]

[0001] Related Applications This application claims the benefit of, and priority to, U.S. Provisional Application No. 62 / 695,920, filed July 10, 2018, and U.S. Provisional Application No. 62 / 835,543, filed April 18, 2019, the entire contents of each of which are incorporated herein by reference in their entirety.

[0002] The present disclosure relates to 3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione compounds and compositions and their uses for treating IKAROS family zinc finger 2 (IKZF2)-dependent diseases or disorders or where reducing IKZF2 or IKZF4 protein levels can ameliorate the disease or disorder. [Background technology]

[0003] IKAROS family zinc finger 2 (IKZF2), also known as Helios, is one of five members of the Ikaros family of transcription factors found in mammals. IKZF2 contains four zinc finger domains near the N-terminus involved in DNA binding and two zinc finger domains at the C-terminus involved in protein dimerization. IKZF2 is approximately 50% identical to the Ikaros family members Ikaros (IKZF1), Aiolos (IKZF3) and Eos (IKZF4), with the highest homology (80%+ identity) in the zinc finger region. These four Ikaros family transcription factors bind to the same DNA consensus site and can heterodimerize with each other when coexpressed in cells. The fifth Ikaros family protein, Pegasus (IKZF5), is only 25% identical to IKZF2, binds to a different DNA site than other Ikaros family members, and does not readily heterodimerize with other Ikaros family proteins. IKZF2, IKZF1, and IKZF3 are expressed primarily in hematopoietic cells, whereas IKZF4 and IKZF5 are expressed in a variety of tissues. (John, LB, et al., (2011), Mol. Immunol. 48: 1272-1278; Perdomo, J., et al., (2000), J. Biol. Chem. 275: 38347-38354).

[0004] IKZF2 is believed to have a critical role in regulatory T cell (Treg) function and stability. IKZF2 is highly expressed at the mRNA and protein levels by regulatory T cell populations. Knockdown of IKZF2 by siRNA has been shown to result in downregulation of FoxP3 and impair the ability of isolated human CD4+CD25+ Tregs to block T cell activation in vitro. Furthermore, overexpression of IKZF2 in isolated mouse Tregs has been shown to increase the expression of Treg-associated markers such as CD103 and GITR, and IKZF2-overexpressing cells showed increased suppression of responder T cells. IKZF2 has also been found to bind to the promoter of FoxP3, a transcription factor that defines the regulatory T cell lineage, and affect FoxP3 expression.

[0005] Knockout of IKZF2 in FoxP3-expressing Tregs in mice has been shown to cause activated Tregs to lose inhibitory properties, express T effector cytokines, and take over T effector function. 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 thought to be cell-intrinsic, since Rag2- / - mice fed bone marrow from IKZF2 knockout mice, but not from IKZF2+ / +, develop autoimmune disease. Direct evidence that IKZF2 affects regulatory T cell function was provided by analysis of mice with deletion of IKZF2 exclusively in FoxP3-expressing cells (FoxP3-YFP-Cre Heliosfl / fl). Results showed that the mice also develop autoimmune disease with similar characteristics as observed in whole animal IKZF2 knockouts. Furthermore, pathway analysis of CHIP-SEQ experiments also suggests that IKZF2 influences the expression of genes in the STAT5 / IL-2Rα pathway in regulatory T cells. This effect of IKZF2 deficiency was shown to be more evident after immune challenge (viral infection or sheep blood injection), and it was observed that after immune stimulation, IKZF2 negative regulatory T cells began to take on the characteristics 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, HJ., et al., (2015), Science 350: 334-339; Nakawaga, H., et al., (2016) PNAS, 113: 6248-6253).

[0006] Overexpression of Ikaros isoforms lacking the DNA binding domain has been shown to be associated with multiple human hematological malignancies. Recently, mutations in the IKZF2 gene resulting in aberrant splicing variants have been identified in adult T-cell leukemia and hypodiploid acute lymphoblastic leukemia. These isoforms capable of dimerization have been proposed to exert a dominant negative effect on the Ikaros family of transcription factors stimulating lymphoma development. IKZF2 knockout mutants that survive to adulthood do not develop lymphoma, 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).

[0007] Currently, anti-CTLA4 antibodies are used in the clinic to target Tregs in tumors. However, targeting CTLA4 frequently results in systemic activation of T effector cells, resulting in excessive toxicity and limiting its therapeutic utility. Up to three-quarters of patients treated with the combination of anti-PD1 and anti-CTLA4 report adverse events of grade 3 or higher. (National Cancer Institute, Division of Cancer Treatment & Diagnosis, Common Terminology for Adverse Events (CTCAE), https: / / ctep.cancer.gov / protocolDevelopment / electronic_applications / ctc.htm). Thus, there is a strong need to provide compounds that target Tregs in tumors without causing systemic activation of T effector cells.

[0008] IKZF2-specific degraders may focus enhanced immune responses in tumor or near-tumor areas, potentially providing better tolerated and less toxic therapeutic agents for the treatment of cancer. Summary of the Invention [Means for solving the problem]

[0009] The compounds of the present disclosure have utility as therapeutic agents, particularly for cancer and related diseases. In one aspect, the compounds of the present disclosure have IKZF2 degrading activity, preferably at or below 50 μM level, more preferably at or below 10 μM level. In another aspect, the compounds of the present disclosure have degrading activity against IKZF2 that is selective for one or more of IKZF1, IKZF3, IKZF4 and / or IKZF5. In another aspect, the compounds of the present disclosure have degrading activity against both IKZF2 and IKZF4. The compounds of the present disclosure have utility in the treatment of cancer and other diseases where such degrading activity would be beneficial to the patient. For example, without being bound by any theory, the inventors believe that by reducing the level of IKZF2 in tumor Tregs, the patient's immune system may be able to attack the disease more effectively. In summary, the present disclosure provides novel IKZF2 degrading agents that are useful in the treatment of cancer and other diseases.

[0010] A first aspect of the present disclosure is a compound of formula (I') [ka] (In the formula, X 1 and X 2 are independently H, (C 1 ~C 4 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, (C 3 ~C7 ) cycloalkyl, halogen, -CN, -OH, or -NH 2 and R x is H or D, R 1 teeth, [ka] and Each R 2 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 or The Two R's 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S; or R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 4- to 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 3 is (C 1 ~C 6) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, or -NH 2 and R 4 -OR 5 or -NR 6 R 6’ and R 5 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forming a 4-8 membered heterocycloalkyl ring optionally substituted with R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 4- to 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 4 R 9 and optionally replaced by Each R 8 independently, each occurrence represents a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) Haloalkoxy, -CN, -OH, -NR 13R 14 , -NH 2 , -O(C 3 ~C 7 )cycloalkyl, —O-4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, —O(C 6 ~C 10 ) aryl, or -O-5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkoxy is selected from 1 to 3 R 10 cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1 to 3 R 11 or The Two R's 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, or two R 8 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, or two R 8 form =(O) with the same atom to which they are attached, Each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, (C 3 ~C 6 ) Cycloalkyl, -OH, -CN, -NH 2 , or -NR 13 R 14 or The Two R's 9along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 4 ~C 7 ) a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, or two R 9 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; Each R 10 are independently calculated for each occurrence, (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; Each R 11 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, and -NH 2 is selected from Each R 12 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6) haloalkoxy, halogen, -OH, -CN, or -NH 2 and The Two R's 12 along with the atoms to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; R 13 and R 14 are each independently: (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; The Two R's 15 along with the atoms to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 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, where s+n is ≦4. or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0011] In one embodiment, the present disclosure provides a compound of formula (I') having the structure of formula (I): [ka] (In the formula, R x is H or D, R1 teeth, [ka] and Each R 2 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 or The Two R's 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S; or R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6) haloalkoxy, halogen, -OH, or -NH 2 and R 4 -OR 5 or -NR 6 R 6’ and R 5 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8forming a 4- to 7-membered heterocycloalkyl ring optionally substituted with R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 4 R 9 and optionally replaced by Each R 8 independently, each occurrence represents a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, -CN, -OH, or -NH 2 where alkoxy is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10) optionally substituted with 1 to 3 substituents independently selected from aryl, and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; The Two R's 8 along with the atoms to which they are attached (C 5 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; Each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 or The Two R's 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 5 ~C 7 ) forming a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 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, where s+n is ≦4. or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0012] In another aspect, the present disclosure provides a compound of formula (I') or formula (I') or formula (I), R x is H or D, R 1 teeth, [ka] and Each R 2 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 or The Two R's 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S; or R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, or -NH 2 and R 4 -OR 5 or -NR 6 R 6’ and R 5 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forming a 4- to 7-membered heterocycloalkyl ring optionally substituted with R2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 4 R 9 and optionally replaced by Each R 8 independently, each occurrence represents a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -CN, -OH, or -NH 2 or The Two R's 8 along with the atoms to which they are attached (C 5 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; Each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 or The Two R's 9along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 5 ~C 7 ) forming a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 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, where s+n is ≦4. or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0013] In one embodiment of the disclosure, hydrogen in formula (I') or a compound of formula (I') is present in normal isotopic abundance. In preferred embodiments of the disclosure, hydrogen is isotopically enriched with deuterium (D), and in particularly preferred embodiments of the invention, hydrogen is isotopically enriched with deuterium (D) at position R, as discussed in more detail below with respect to isotopes and isotopic enrichment. x The hydrogen is enriched in D.

[0014] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof and a pharma- ceutically acceptable carrier or excipient. The pharmaceutical composition is useful for treating IKZF2-dependent diseases or disorders. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

[0015] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharma- ceutically acceptable carrier or excipient, for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder. The pharmaceutical composition is useful for treating an IKZF2-dependent disease or disorder. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

[0016] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof and a pharma- ceutically acceptable carrier or excipient. The pharmaceutical composition is useful for treating a disease or disorder affected by a decrease in IKZF2 protein level. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

[0017] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharma- ceutically acceptable carrier or excipient, for use in treating a disease or disorder affected by a decrease in IKZF2 protein level, wherein the decrease in IKZF2 protein level treats the disease or disorder. The pharmaceutical composition may further comprise at least one additional pharmaceutical agent.

[0018] In another aspect, the disclosure relates to a method of degrading IKZF2, the method comprising administering to a patient in need thereof a compound of Formula (I') or Formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0019] Another aspect of the present disclosure relates to a method of modulating IKZF2 protein levels, comprising administering to a patient in need thereof a compound of Formula (I') or Formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0020] In another aspect, the disclosure relates to a method of decreasing IKZF2 protein levels, comprising administering to a patient in need thereof a compound of Formula (I') or Formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0021] In another aspect, the disclosure relates to a method of decreasing IKZF2 protein levels, comprising administering to a patient in need thereof a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0022] Another aspect of the present disclosure relates to a method of reducing cell proliferation, comprising administering to a patient in need thereof a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and reducing IKZF2 protein levels.

[0023] In another aspect, the disclosure relates to a method of decreasing IKZF2 protein levels, comprising administering to a patient in need thereof a compound of Formula (I') or Formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0024] In another aspect, the present disclosure relates to a method for treating cancer, comprising administering to a patient in need thereof a compound of formula (I') or formula (I) or its pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer.In one embodiment, the cancer is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, colon cancer, skin 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC). In another embodiment, the cancer is an immune-deficient or immunogenic cancer.

[0025] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharma- ceutically acceptable carrier or excipient, for use in treating an IKZF2-dependent disease or disorder.

[0026] In another aspect, the present invention relates to the use of a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharma- ceutically acceptable carrier or excipient in the manufacture of a medicament, for treating an IKZF2-dependent disease or disorder.

[0027] Another aspect of the present disclosure relates to a method of treating an IKZF2-dependent disease or disorder, comprising 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharma- ceutically acceptable carrier or excipient.

[0028] In another aspect, the disclosure relates to a method of treating an IKZF2-dependent disease or disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0029] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of an IKZF2-dependent disease or disorder.

[0030] In another aspect, the disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder.

[0031] Another aspect of the present disclosure relates to a method of treating a disease or disorder affected by modulation of IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0032] In another aspect, the disclosure relates to a method of treating a disease or disorder affected by decreased IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0033] Another aspect of the present disclosure relates to a method of treating a disease or disorder affected by decreased IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0034] In another aspect, the disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment of a disease or disorder affected by modulation of IKZF2 protein levels.

[0035] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment of a disease or disorder affected by reduced IKZF2 protein levels.

[0036] In another aspect, the disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment of a disease or disorder affected by decreased IKZF2 protein levels.

[0037] In another aspect, the disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by modulation of IKZF2 protein levels.

[0038] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by decreased IKZF2 protein levels.

[0039] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by decreased IKZF2 protein levels.

[0040] In another aspect, the disclosure relates to a method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the cancer is an immune response deficient cancer or an immunogenic cancer.

[0041] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically 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 regulation of IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0042] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease or disorder associated with the regulation of IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0043] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically 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 decreased IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0044] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease or disorder associated with decreased IKZF2 protein levels. In one embodiment, the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0045] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically 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 level. In one embodiment, the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0046] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease or disorder associated with a decrease in IKZF2 protein level. In one embodiment, the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0047] Another aspect of the present disclosure relates to a method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (F) or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the cancer is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0048] In another aspect, the disclosure relates to a compound of Formula (F') or Formula (I) or a pharma- ceutically 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 cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0049] Another aspect of the disclosure relates to the use of a compound of Formula (I') or Formula (I) or a pharma- ceutically 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 cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0050] In another aspect, the disclosure relates to a method of treating a disease or disorder affected by modulation of IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0051] Another aspect of the present disclosure relates to a method of treating a disease or disorder affected by decreased IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0052] In another aspect, the disclosure relates to a method of treating a disease or disorder affected by decreased IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0053] In another aspect, the disclosure relates to a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of a disease or disorder affected by modulation of IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0054] Another aspect of the present disclosure relates to a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0055] In another aspect, the disclosure relates to a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0056] In another aspect, the disclosure relates to the use of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by modulation of IKZF2 levels, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0057] Another aspect of the present disclosure relates to the use of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0058] In another aspect, the disclosure relates to the use of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC).

[0059] In another aspect, the present disclosure relates to a method for treating a disease or disorder affected by modulation of IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0060] Another aspect of the present disclosure relates to a method for treating a disease or disorder affected by decreased IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0061] In another aspect, the present disclosure relates to a method for treating a disease or disorder affected by a decrease in IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0062] In another aspect, the disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of a disease or disorder affected by modulation of IKZF2 protein levels, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0063] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of a disease or disorder affected by reduced IKZF2 protein levels, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0064] In another aspect, the disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment of a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0065] In another aspect, the disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for the treatment of a disease or disorder affected by modulation of IKZF2 protein levels, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0066] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for the treatment of a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0067] In another aspect, the disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for the treatment of a disease or disorder affected by decreased IKZF2 protein levels, wherein the disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0068] In another aspect, the disclosure relates to a method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the cancer is an immune response deficient cancer or an immunogenic cancer.

[0069] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment of immune response deficient or immunogenic cancer.

[0070] In another aspect, the disclosure relates to the use of a compound of Formula (I') or Formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating an immune response-deficient or immunogenic cancer.

[0071] Another aspect of the present disclosure relates to a method for treating an IKZF2-dependent disease or disorder by regulating 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0072] In another aspect, the present disclosure relates to a method for treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0073] Another aspect of the present disclosure relates to a method for 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0074] Another aspect of the present disclosure relates to a method for treating an IKZF2-dependent disease or disorder by regulating 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0075] In another aspect, the present disclosure relates to a method for treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, comprising 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0076] Another aspect of the present disclosure relates to a method for 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0077] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0078] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0079] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by regulating IKZF2 protein levels, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0080] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels, wherein modulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0081] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0082] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0083] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically 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 reducing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0084] 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 pharma- ceutically 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 the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0085] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically 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 modulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0086] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of an IKZF2-dependent disease or disorder by regulating IKZF2 protein levels, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0087] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically 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 the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0088] 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 pharma- ceutically 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 the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0089] Another aspect of the present disclosure relates to a method for treating a disease or disorder by reducing IKZF2 protein levels, comprising 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0090] In another aspect, the present disclosure relates to a method for treating a disease or disorder by reducing IKZF2 protein levels, comprising administering to a subject in need thereof a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein reducing IKZF2 protein levels treats the disease or disorder.

[0091] Another aspect of the present disclosure relates to a method for treating a disease or disorder by regulating 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein regulating IKZF2 protein levels treats the disease or disorder.

[0092] In another aspect, the present disclosure relates to a method for treating a disease or disorder by regulating IKZF2 protein levels, comprising the step of administering to a subject in need thereof a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein regulating IKZF2 protein levels treats the disease or disorder.

[0093] Another aspect of the present disclosure relates to a method for 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0094] In another aspect, the present disclosure relates to a method for treating a disease or disorder by reducing IKZF2 protein levels, comprising administering to a subject in need thereof a compound of Formula (I') or Formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0095] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0096] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0097] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by regulating IKZF2 protein levels, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0098] In another aspect, the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by modulating IKZF2 protein levels, wherein modulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0099] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0100] In another aspect, the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0101] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in treating a disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the disease or disorder.

[0102] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating a disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the disease or disorder.

[0103] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in treating a disease or disorder by modulating IKZF2 protein levels, wherein modulating IKZF2 protein levels treats the disease or disorder.

[0104] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating a disease or disorder by modulating IKZF2 protein levels, wherein modulating IKZF2 protein levels treats the disease or disorder.

[0105] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in treating a disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0106] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating a disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0107] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0108] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0109] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder by regulating IKZF2 protein levels, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0110] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder by regulating IKZF2 protein levels, wherein regulating IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0111] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0112] 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 pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the IKZF2-dependent disease or disorder.

[0113] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically 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 reducing IKZF2 protein levels treats the disease or disorder.

[0114] 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 pharma- ceutically 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 the reduction in IKZF2 protein levels treats the disease or disorder.

[0115] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically 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 modulating IKZF2 protein levels treats the disease or disorder.

[0116] 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 pharma- ceutically 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 modulating IKZF2 protein levels treats the disease or disorder.

[0117] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically 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 the reduction in IKZF2 protein levels treats the disease or disorder.

[0118] 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 pharma- ceutically 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 the reduction in IKZF2 protein levels treats the disease or disorder.

[0119] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in treating a disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the disease or disorder.

[0120] In another aspect, the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in treating a disease or disorder by modulating IKZF2 protein levels, wherein modulating IKZF2 protein levels treats the disease or disorder.

[0121] Another aspect of the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in treating a disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0122] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease or disorder by reducing IKZF2 protein levels, wherein reducing IKZF2 protein levels treats the disease or disorder.

[0123] In another aspect, the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease or disorder by modulating IKZF2 protein levels, wherein modulating IKZF2 protein levels treats the disease or disorder.

[0124] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease or disorder by reducing IKZF2 protein levels, wherein the reduction in IKZF2 protein levels treats the disease or disorder.

[0125] In another aspect of the disclosure, a compound according to the disclosure is formulated into a pharmaceutical composition comprising an effective amount, preferably a pharma- ceutical effective amount, of a compound according to the disclosure or a salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharma- ceutically acceptable excipient or carrier.

[0126] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the manufacture of a medicament for treating an IKZF2-dependent disease or disorder.

[0127] In another aspect, the present disclosure relates to a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the manufacture of a medicament for treating a disease associated with the regulation of IKZF2 protein levels.

[0128] Another aspect of the present disclosure relates to the use of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the treatment of a disease associated with the regulation of IKZF2 protein levels.

[0129] In some embodiments of the methods disclosed herein, the administration of the compound of Formula (I') or Formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, is performed orally, parenterally, subcutaneously, by injection, or by infusion.

[0130] 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 modulation of IKZF2 protein levels, and in the treatment of IKZF2-dependent diseases or disorders.

[0131] In one embodiment, the disease or disorder that can be treated by the compounds of the present disclosure is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcoma selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, Ewing's sarcoma, non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid 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 carcinoma (NPC), and microsatellite-stable colorectal cancer (mssCRC). In another embodiment, the IKZF2-dependent disease or disorder is a cancer with a deficient immune response or an immunogenic cancer.

[0132] The present disclosure provides agents with a novel mechanism of action against the IKZF2 protein in the treatment of various types of diseases, including cancer and metastasis, diseases affected by modulation of IKZF2 protein levels, and IKZF2-dependent diseases or disorders.Finally, the present disclosure provides the medical community with novel pharmacological strategies for the treatment of diseases and disorders associated with the IKZF2 protein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0133] The present disclosure relates to compounds and compositions that can modulate IKZF2 protein levels. The present disclosure features a method for treating, preventing, or ameliorating a disease or disorder in which IKZF2 plays a role by administering a therapeutically effective amount of a compound of formula (I') or formula (I) or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to a patient in need thereof. The method of the present disclosure can be used to treat a variety of IKZF2-dependent diseases and disorders by modulating IKZF2 protein levels. Modulating IKZF2 protein levels by degradation provides a novel approach to the treatment, prevention, or amelioration of diseases, including, but not limited to, cancer and metastasis, and other IKZF2-dependent diseases or disorders.

[0134] In one embodiment, the compounds of the present disclosure have utility as therapeutic agents, particularly for cancer and related diseases. In one embodiment, the compounds of the present disclosure have IKZF2 degrading activity, preferably at or below 50 μM level, more preferably at or below 10 μM level. In another embodiment, the compounds of the present disclosure have degrading activity against IKZF2 that is selective for one or more of IKZF1, IKZF3, IKZF4 and / or IKZF5. In another embodiment, the compounds of the present disclosure have degrading activity against both IKZF2 and IKZF4. The compounds of the present disclosure have utility in the treatment of cancer and other diseases where such degrading activity would be beneficial to the patient. For example, without being bound by any theory, the inventors believe that by reducing the level of IKZF2 in tumor Tregs, the patient's immune system may be able to attack the disease more effectively. In summary, the present disclosure provides novel IKZF2 degrading agents that are useful in the treatment of cancer and other diseases.

[0135] In a first aspect of the present disclosure, a compound of formula (I'): [ka] (In the formula, R x , X 1 , X 2 and R1 is as above) or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers and tautomers thereof are described.

[0136] Details of the present disclosure are described 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, exemplary methods and materials are described herein. Other features, objects, and advantages of the present disclosure will be apparent from the description and claims. In this specification and the appended claims, the singular form includes the plural form unless the context clearly indicates otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. All patents and publications cited herein are incorporated herein by reference in their entirety.

[0137] Definitions of terms and rules used Terms not specifically defined herein should be given the meaning that would be given to them by one of ordinary skill in the art in view of the disclosure and context. However, as used in this specification and the appended claims, unless specified to the contrary, the following terms have the meaning indicated and the following provisions shall be observed.

[0138] A. Chemical Nomenclature, Terminology and Conventions In the groups, radicals or substructures defined below, the number of carbon atoms is often specified before the group. For example, (C 1 ~C 10) alkyl means an alkyl group or radical having 1 to 10 carbon atoms. In general, for groups containing more than one subgroup, the last listed group is the radical attachment point. For example, "alkylaryl" means a monovalent radical of the formula alkyl-aryl-, and "arylalkyl" means a monovalent radical of the formula aryl-alkyl-. Furthermore, where a divalent radical is appropriate, the use of a term designating a monovalent radical shall be construed to designate the respective divalent radical, and vice versa. Unless otherwise indicated, conventional definitions of terminology and conventional stable valences may be presumed and achieved in all formulas and groups. The articles "a" and "an" mean one or more than one (e.g., at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0139] The term "and / or" means "and" or "or" unless otherwise stated.

[0140] The term "optionally substituted" means that a given chemical moiety (e.g., an alkyl group) can (but does not require) be attached to other substituents (e.g., heteroatoms). For example, an optionally substituted alkyl group can be a fully saturated alkyl chain (e.g., pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have a substituent other than hydrogen. For example, it can be attached at any point along the chain to a halogen atom, a hydroxyl group, or any other substituent described herein. Thus, the term "optionally substituted" means that a given chemical moiety may contain other functional groups, but does not necessarily have any additional functional groups. Suitable substituents for use in any substitution of the described groups include halogen, oxo, -OH, -CN, -COOH, -CH 2 CN, -O-(C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, -O-(C 2 ~C 6 ) alkenyl, -O-(C 2 ~C 6 ) alkynyl, (C 2 ~C 6 ) alkenyl, (C 2 ~C 6 ) Alkynyl, -OH, -OP(O)(OH) 2 , -OC(O)(C 1 ~C 6 ) alkyl, -C(O)(C 1 ~C 6 ) alkyl, -OC(O)O(C 1 ~C 6 ) Alkyl, -NH 2 , -NH((C 1 ~C 6 ) alkyl), -N((C 1 ~C 6 )Alkyl) 2 , -NHC(O)(C 1 ~C 6 ) alkyl, -C(O)NH(C 1 ~C 6 ) alkyl, -S(O) 2 (C 1 ~C 6 ) alkyl, -S(O)NH(C 1 ~C 6 ) alkyl and S(O)N((C 1 ~C 6 )Alkyl) 2 The substituents may themselves be optionally substituted. As used herein, "optionally substituted" also refers to substituted or unsubstituted, the meanings of which are described below.

[0141] The term "substituted" means that a particular group or moiety has one or more suitable substituents, and that the substituents may be attached to the particular group or moiety at one or more positions. For example, an aryl substituted with a cycloalkyl may indicate that the cycloalkyl is attached to an aryl atom or fused to the aryl, such that they are attached by sharing two or more common atoms.

[0142] The term "unsubstituted" means that the specified group bears no substituents.

[0143] Unless otherwise defined, "aryl" refers to a cyclic aromatic hydrocarbon group having one to three aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. When containing two aromatic rings (such as bicyclic), the aromatic rings of the aryl group are optionally bonded (e.g., biphenyl) or fused (e.g., naphthyl) at a single point. Aryl groups are optionally substituted at any point of attachment with one or more substituents, for example, 1 to 5 substituents. Exemplary substituents include -H, -halogen, -CN, -O-(C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkyl, -O-(C 2 ~C 6 ) alkenyl, -O-(C 2 ~C 6 ) alkynyl, (C 2 ~C 6 ) alkenyl, (C 2 ~C 6 ) Alkynyl, -OH, -OP(O)(OH) 2 , -OC(O)(C 1 ~C 6 ) alkyl, -C(O)(C 1 ~C 6 ) alkyl, -OC(O)O(C 1 ~C 6 ) Alkyl, NH 2 , NH((C 1 ~C 6 ) alkyl), N(((C 1 ~C 6 )Alkyl) 2, -S(O) 2 -(C 1 ~C 6 ) alkyl, -S(O)NH(C 1 ~C 6 ) alkyl and S(O)N((C 1 ~C 6 )Alkyl) 2 The substituents are themselves optionally substituted. In addition, when containing two fused rings, the aryl group has an unsaturated or partially saturated ring fused to an optionally 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.

[0144] Unless otherwise indicated, "heteroaryl" means a monovalent monocyclic or polycyclic aromatic radical of 5 to 24 ring atoms containing one or more ring heteroatoms selected from N, O, or S, with the remaining ring atoms being C. As defined herein, heteroaryl is also a bicyclic aromatic heterocyclic radical in which the heteroatoms are selected from N, O, or S. The aromatic radicals are optionally substituted independently with one or more substituents described herein. Examples include 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, isopropyl ... midazo[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, Indolinyl, 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, quinazo Linyl, 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-1Δ 2-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, benzoxazolyl, benzisoxazolyl, 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[5,4d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl and derivatives thereof. Additionally, when containing two fused rings, an aryl group as defined herein may have an unsaturated or partially saturated ring fused to 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.

[0145] Halogen or "halo" means fluorine, chlorine, bromine or iodine.

[0146] "Alkyl" means a straight or branched chain saturated hydrocarbon containing 1 to 12 carbon atoms. 1 ~C 6) Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

[0147] "Alkoxy" means a straight or branched chain saturated hydrocarbon containing 1 to 12 carbon atoms in the chain including a terminal "O", e.g., -O(alkyl). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, t-butoxy, or pentoxy groups.

[0148] "Alkenyl" means a straight or branched chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. An "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 can be straight or branched.

[0149] "Alkynyl" refers to a straight or branched chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. An "alkynyl" group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propargyl, n-butynyl, isobutynyl, pentynyl, or hexynyl. Alkynyl groups can be unsubstituted or substituted.

[0150] "Cycloalkyl" or "carbocyclyl" means a monocyclic or polycyclic saturated carbocyclic ring containing 3 to 18 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl, and derivatives thereof. (C 3 ~C 8) Cycloalkyl is a cycloalkyl group containing 3 to 8 carbon atoms. The cycloalkyl groups can be fused (e.g., decalin) or bridged (e.g., norvoman).

[0151] "Heterocyclyl" or "heterocycloalkyl" refers to 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 having no delocalized n-electrons (aromaticity) shared between the ring carbons or heteroatoms. The heterocycloalkyl ring structure may be substituted with one or more substituents. The substituents may 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.

[0152] "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, and the like.

[0153] "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, and the like.

[0154] "Cyano" refers to a substituent having a carbon atom attached to a nitrogen atom by a triple bond, e.g., C≡N.

[0155] "Amino" refers to a substituent that contains at least one nitrogen atom, such as NH 2 )

[0156] "Hydroxyalkyl" refers to an alkyl group substituted with one or more -OH groups. Examples of hydroxyalkyl groups include HO-CH 2 -,HO-CH 2 CH 2 - and CH 2 Contains -CH(OH)-.

[0157] "Spirocycloalkyl" or "spirocyclyl" refers to a carbogen bicyclic ring system in which both rings are bonded through a single atom. The size and nature of the rings can be different or can be the same in size and nature. Examples include spiropentane, spriohexane, spiroheptane, spirooctane, spirononane or spirodecane. One or both rings of the spiro ring can be fused to a carbocyclic, heterocyclic, aromatic or heteroaromatic ring of another ring. (C 3 ~C 12 ) A spirocycloalkyl is a spiro ring containing 3 to 12 carbon atoms.

[0158] "Spiroheterocycloalkyl" or "spiroheterocyclyl" means a spirocycle in which at least one ring is a heterocycle, and one or more carbon atoms may be replaced with a heteroatom (e.g., one or more carbon atoms may be replaced with a heteroatom in at least one ring). One or both rings of the spiroheterocycle may be fused to a carbocyclic, heterocyclic, aromatic or heteroaromatic ring of another ring.

[0159] B. Terminology and Rules for Salts, Prodrugs, Derivatives and Solvates "Prodrug" or "prodrug derivative" refers to a covalent derivative or carrier of a parent compound or active drug that undergoes at least some degree of biotransformation before exhibiting its pharmacological effect. Generally, such prodrugs have metabolically cleavable groups that are rapidly converted in vivo to generate the parent compound, for example by hydrolysis in blood, and generally include ester and amide analogs of the parent compound. Prodrugs are formulated for improved chemical stability, improved patient acceptance and compliance, improved bioavailability, extended duration of action, improved organ selectivity, improved formulation (e.g., increased aqueous solubility), and / or reduced side effects (such as toxicity). Generally, the prodrug itself has weak or no biological activity and is stable under normal conditions.Prodrugs can be prepared by methods well known in the art, for example, A Textbook of Drug Design and Development, Krogsgaard-Larsen and H. Bundgaard (eds.), Gordon & Breach, 1991, especially Chapter 5: “Design and Applications of Prodrugs”; Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985; Prodrugs: Topical and Ocular Drug Delivery, KB Loan (ed.), Marcel Dekker, 1998; Methods in Enzymology, K. Widder et al. (eds.), Vol. 42, Academic Press, 1985, especially pp. 309-396; Burger's Medicinal Chemistry and Drug Discovery, 5th Ed., M. Wolff (ed.), John Wiley & Sons, 1995, especially 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, EB Roche (ed.), Elsevier, 1987, each of which is incorporated herein by reference in its entirety.

[0160] As used herein, "pharmaceutically acceptable prodrugs" means prodrugs of the compounds of the present disclosure that are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, within the scope of sound medical judgment, commensurate with a reasonable benefit / risk ratio, and where possible are as effective for their intended use as the zwitterionic form.

[0161] "Salt" refers to the ionic form of the parent compound or the product of the reaction of the parent compound with a suitable acid or base to make an acid or base salt of the parent compound. The salts of the compounds of the present disclosure can be synthesized from the parent compound that contains a basic or acidic moiety by conventional chemical methods. In general, salts are prepared by reacting the free base or acid parent compound with a stoichiometric amount or an excess of the desired salt-forming inorganic or organic acid or base in an appropriate solvent, or various combinations of solvents.

[0162] "Pharmaceutically acceptable salt" means a salt of a compound of the present disclosure that is suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reactions, and the like, within the scope of sound medical judgment, commensurate with a reasonable benefit / risk ratio, and is usually water- or oil-soluble or dispersible and effective for its intended use. This term includes pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. The compounds of the present disclosure are useful in both free base and salt form, so that in practice, the use of the salt form is equivalent to the use of the base form. Lists of suitable salts can be found, for example, in SMBirge et al., J.Pharm.Sci., 1977,66,pp.1-19, the contents of which are incorporated herein by reference in their entirety.

[0163] "Pharmaceutically acceptable acid addition salts" refers to salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, nitric acid, phosphoric acid, and the like, as well as salts of 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, hemisulfuric acid, heptasulfuric acid, glycerol ... In some embodiments, the salts are formed with organic acids such as carboxylic 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, salicylic acid, stearic acid, succinic acid, sulfanilic acid, tartaric acid, p-toluenesulfonic acid, undecanoic acid, and the like.

[0164] By "pharmacologically acceptable base addition salts" is meant salts formed with inorganic bases such as ammonia or hydroxides, carbonates or bicarbonates of ammonia or metal cations of sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese, aluminum and the like which retain the biological effectiveness and properties of the free acids and are not biologically or otherwise undesirable. Ammonium, potassium, sodium, calcium and magnesium salts are particularly preferred. Salts derived from pharmaceutically acceptable organic non-toxic bases include primary, secondary and tertiary amines, quaternary amine compounds, substituted amines including naturally occurring substituted amines, cyclic amines and methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, TEA, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydrabamine, coli, ketone ... The preferred organic non-toxic bases include salts of basic ion exchange resins such as amines, betaines, ethylenediamines, glucosamines, methylglucamines, theobromines, purines, piperazines, piperidines, N-ethylpiperidines, tetramethylammonium compounds, tetraethylammonium compounds, pyridines, N,N-dimethylanilines, N-methylpiperidines, N-methylmorpholines, dicyclohexylamines, dibenzylamines, N,N-dibenzylphenethylamines, 1-ephenamines, N,N'-dibenzylethylenediamines, polyamine resins, and the like. Particularly preferred organic non-toxic bases are isopropylamines, diethylamines, ethanolamines, trimethylamines, dicyclohexylamines, choline, and caffeine.

[0165] "Solvate" refers to a complex of variable stoichiometry formed by a solute, such as a compound of formula (I') or formula (I), and a solvent, such as water, ethanol, or acetic acid. This physical association may include varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate is capable of isolation, for example when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. In general, such solvents selected for the purposes of the disclosure do not interfere with the biological activity of the solute. Solvates include both solution-phase solvates and isolable solvates. Representative solvates include hydrates, ethanolates, methanolates, and the like.

[0166] "Hydrate" means a solvate where the solvent molecule is water.

[0167] The compounds of the present disclosure discussed below, including the free base or acids thereof, their salts, solvates and prodrugs, may contain oxidized sulfur atoms or quaternized nitrogen atoms in their structure, particularly pharma- ceutically acceptable forms thereof, although not specifically stated or shown. Such forms, particularly pharma- ceutically acceptable forms, are intended to be encompassed by the appended claims.

[0168] C. Isomerism Terminology and Rules "Isomers" mean compounds that have the same number and kind of atoms, and hence the same molecular weight, but differ with regard to the arrangement or configuration of the atoms in space. The term includes stereoisomers and geometric isomers.

[0169] "Stereoisomer" or "optical isomer" refers to a stable isomer that has at least one chiral atom or restricted rotation resulting in a vertical asymmetric plane (e.g., certain biphenyls, arenes, spiro compounds, etc.) that can rotate plane-polarized light. Asymmetric centers and other chemical structures may exist in the compounds of the present disclosure, which may result in stereoisomerism, the present disclosure contemplates stereoisomers and mixtures thereof. The compounds of the present disclosure and their salts contain asymmetric carbon atoms and therefore may exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. Typically, such compounds are prepared as racemic mixtures. However, if desired, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures. As described in more detail below, individual stereoisomers of the compounds are prepared by synthesis from optically active starting materials containing the desired chiral center, or by conversion to a diastereomeric mixture followed by separation or resolution after preparation of a mixture of enantiomeric products, such as by separation or recrystallization, chromatographic techniques, the use of chiral resolving agents, or by direct separation of the enantiomers on a chiral chromatographic column. Starting compounds of particular stereochemistry are either commercially available or made by the methods described below, and resolved by techniques well known in the art.

[0170] "Enantiomers" means a pair of stereoisomers that are non-superimposable mirror images of each other.

[0171] "Diastereoisomers" or "diastereomers" mean optical isomers that are not mirror images of each other.

[0172] A "racemic mixture" or "racemate" means a mixture containing equal amounts of individual enantiomers.

[0173] "Non-racemic mixture" means a mixture containing unequal amounts of individual enantiomers.

[0174] "Geometric isomers" are isomers that are stabilized due to restricted freedom of rotation by double bonds (e.g., cis-2-butene and trans-2-butene) or cyclic structures (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 present disclosure, the present disclosure contemplates each of the various stable geometric isomers and mixtures thereof resulting from the arrangement of substituents around these double bonds and within these cyclic structures. Substituents and isomers are designated using the conventional method of cis / trans or E or Z notation. The term "E" refers to higher order substituents on opposite sides of a double bond and the term "Z" refers to higher order substituents on the same side of a 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 incorporated herein by reference in its entirety. Some of the examples below represent single E isomers, single Z isomers, and E / Z isomer mixtures. Determination of E and Z isomers can be performed using techniques such as X-ray crystallography, 1 H NMR and 13 This can be done by analytical methods such as C NMR.

[0175] Some of the compounds of the present disclosure may exist in two or more tautomeric forms, and as stated above, the compounds of the present disclosure include all such tautomers.

[0176] It is well known in the art that the biological and pharmacological activity of a compound is highly sensitive to the stereochemistry of the compound. Thus, for example, enantiomers often exhibit significantly different biological activities, including differences in pharmacokinetic properties, including metabolism, protein binding, and the like, and differences in pharmacological properties, including the type of activity exerted, the degree of activity, toxicity, and the like. Thus, one skilled in the art will understand that one enantiomer may be more active or exhibit superior effects when enriched relative to other enantiomers or separated from other enantiomers. Furthermore, one skilled in the art will know how to separate, enrich, or selectively prepare the enantiomers of the compounds of the present disclosure from the knowledge of this disclosure and the prior art.

[0177] Thus, while a racemic drug may be used, it is often less effective than administering an equal amount of the enantiomerically pure drug. In fact, in some cases, one enantiomer may be pharmacologically inactive and merely serve as a simple diluent. For example, ibuprofen was once administered as a racemate, but only the S-isomer of ibuprofen has been shown to be effective as an anti-inflammatory agent (although in the case of ibuprofen, the R-isomer is inactive, but it is converted to the S-isomer in vivo, so the rate of action of the racemic drug is less than that of the pure S-isomer). Furthermore, the pharmacological activity of the enantiomers may have distinct biological activities. For example, S-penicillamine is a treatment for chronic arthritis, but R-penicillamine is toxic. In fact, some purified enantiomers have advantages over the racemate, as the purified individual isomers have been reported to have faster percutaneous penetration rates compared to the racemic mixture. See U.S. Patent Nos. 5,114,946 and 4,818,541.

[0178] Thus, if one enantiomer is more pharmacologically active, less toxic, or has more favorable properties in the body than the other enantiomer, it would be more therapeutically beneficial to administer that enantiomer preferentially. In this way, the patient undergoing treatment would receive a lower total dose of drug and a lower dose of the enantiomer than a potentially toxic or inhibitor of the other enantiomer.

[0179] The preparation of pure enantiomers or mixtures of a desired enantiomeric excess (ee) or enantiomeric purity can be achieved by one or more of many methods: (a) separation or resolution of enantiomers or (b) enantioselective synthesis or combinations thereof well known to those skilled in the art. 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 non-enzymatic kinetic resolution or spontaneous enantioselective crystallization. Such methods are generally elucidated 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 similarly well-known methods for quantification of enantiomeric excess or purity, such as, for example, GC, HPLC, CE or NMR, and for assigning absolute configuration and conformation, such as CD ORD, X-ray crystallography or NMR.

[0180] In general, all tautomers, isomers, and mixtures, whether individual geometric or stereoisomers, or racemic or non-racemic mixtures, of a chemical structure or compound are intended, unless a specific stereochemistry or isomer is specifically indicated in the compound name or structure.

[0181] D. Terminology and Rules for Drug Administration and Treatment A "patient" or "subject" is a mammal, e.g., a human, a mouse, a rat, a guinea pig, a dog, a cat, a horse, a cow, a pig, or a non-human primate, such as a monkey, a chimpanzee, a baboon, or a rhesus monkey. In certain embodiments, the subject is a primate. In yet other embodiments, the subject is a human.

[0182] An "effective amount" or "therapeutically effective amount" when used in reference to a compound means an amount of a compound of the disclosure that (i) treats or prevents a particular disease, condition, or disorder, (ii) alleviates, ameliorates, or eliminates one or more symptoms of a particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder described herein.

[0183] The term "pharmaceutical effective amount" or "therapeutically effective amount" refers to an amount of a compound according to the present disclosure that, when administered to a patient in need thereof, is sufficient to effect treatment of a disease state, condition, or disorder for which the compound has utility. Such an amount will be sufficient to elicit the biological or medical response in a tissue, system, or patient that is desired by the researcher or clinician. The amount of a compound according to the present disclosure that constitutes a therapeutically effective amount will vary depending on 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 or concomitantly with the compound of the present disclosure, and factors such as the age, weight, general condition, sex, and diet of the patient. Such a therapeutically effective amount can be routinely determined by one of ordinary skill in the art having regard to their own knowledge, the prior art, and this disclosure.

[0184] The term "pharmaceutical composition" as used herein refers to a compound of the present disclosure or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof together with at least one pharma- ceutically acceptable carrier in a form suitable for oral or parenteral administration.

[0185] "Carrier" includes carriers, excipients and diluents and means a material, composition or vehicle such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material that contains a pharmaceutical agent, which is involved in the transport or transfer of the pharmaceutical agent from one organ or body part to another organ or body part of a subject.

[0186] 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).

[0187] The terms "inhibit," "inhibition," or "inhibiting," as used herein, refer to the reduction or suppression of a given condition, symptom, or disorder, or disease, or a significant decrease in the underlying activity of a biological activity or biological process.

[0188] As used herein, the terms "treat," "treating," or "treatment" of any disease or disorder refers to alleviating or ameliorating the disease or disorder (i.e., slowing or halting the progression of the disease or at least one of its clinical symptoms); or alleviating or ameliorating at least one physical parameter or biomarker associated with the disease or disorder, including those that may not be discernible by the patient.

[0189] As used herein, the terms "prevent", "preventing" or "prevention" of any disease or disorder refers to the prophylactic treatment of a disease or disorder or the delay in the onset or progression of a disease or disorder.

[0190] By "pharmacologically acceptable" it is meant that the substance or composition must be chemically and / or toxicologically compatible with the other ingredients that make up the formulation and / or the mammal being treated therewith.

[0191] The term "disorder" refers to, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise specified.

[0192] "Administer," "administering," or "administration" means administering a disclosed compound or a pharma- ceutically acceptable salt of a disclosed compound or composition directly to a subject, or administering to a subject a prodrug derivative of the compound, or an analog of the compound, or a pharma- ceutically acceptable salt of the compound, or composition, that is capable of forming an equivalent amount of the active compound in the subject's body.

[0193] "Prodrug" means a compound that is convertible in vivo by metabolic means (eg, by hydrolysis) to a disclosed compound.

[0194] "Compounds of the disclosure", "compounds of formula (I') or formula (I)", "compounds of the disclosure" and equivalent expressions (unless otherwise indicated) refer to all stereoisomers (including diastereoisomers and enantiomers), rotamers, tautomers and isotopically labeled compounds (including deuterium substitutions) as described herein, including formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), and (It), tautomers, prodrugs, salts, particularly pharma- ceutically acceptable salts thereof, and solvates and hydrates thereof, where the context permits, as well as all stereoisomers (including diastereoisomers and enantiomers), rotamers, tautomers and isotopically labeled compounds (including deuterium substitutions), and inherently formed substructures (e.g., polymorphs, solvates and / or hydrates). For the purpose of this disclosure, solvates and hydrates are generally considered as compositions. Generally and preferably, the compounds of this disclosure and formulas specifying the compounds of this disclosure are understood to include only stable compounds and exclude unstable compounds, even if unstable compounds are considered to be literally encompassed by the compound formula. Similarly, reference to intermediates is meant to include their salts and solvates, as far as the context permits, regardless of whether they are claimed as such. For clarity, specific examples may be given in the text where the context permits, but these examples are merely to facilitate understanding and are not intended to exclude other examples where the context permits.

[0195] By "stable compound" or "stable structure" is meant 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, compounds that have "dangling valencies" or are carbanions are not compounds contemplated by the present disclosure.

[0196] In certain embodiments, the term "about" or "approximately" means within 20%, preferably within 10%, and more preferably within 5% of a given value or range.

[0197] The yield of each reaction described herein is expressed as a percentage of the theoretical yield. "Cancer" refers to any cancer caused by the proliferation of malignant neoplastic cells, such as tumors, neoplasms, malignancies of epithelial cells, sarcomas, leukemias, lymphomas, and the like. For example, cancers include, but are not limited to, mesothelioma, leukemia and lymphomas such as cutaneous T-cell lymphoma (CTCL), non-cutaneous peripheral T-cell lymphoma, adult T-cell leukemia / lymphoma (ATLL), B-cell lymphoma, acute non-lymphocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, lymphoma and human T-cell lymphotrophic virus (HTLV) associated lymphomas such as multiple myeloma, non-Hodgkin's lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma, Burkitt's lymphoma, adult T-cell leukemia lymphoma, acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) or hepatocellular carcinoma. Further examples include myelodysplastic syndromes, brain tumors, pediatric solid tumors such as neuroblastoma, retinoblastoma, Wilms' tumor, bone tumors and soft tissue sarcomas, adult common solid tumors such as head and neck cancer (e.g., oral cavity, larynx, nasopharynx, esophagus), genitourinary cancer (e.g., prostate, bladder, kidney, uterus, ovary, testis), 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, gastric cancer, brain tumors, tumors associated with Gorlin's syndrome (e.g., medulloblastoma, meningioma, etc.), and liver cancer, etc. Further exemplary types of cancers that may be treated by the subject compounds include, but are not limited to, skeletal or smooth muscle cancer, gastric cancer, small intestine cancer, rectal cancer, salivary gland cancer, endometrial cancer, adrenal cancer, anal cancer, rectal cancer, parathyroid cancer, and pituitary cancer.

[0198] Additional cancers that the compounds described herein may be useful for preventing, treating, and studying include, for example, colon cancer, familial adenomatous polyposis cancer, and hereditary nonpolyposis colorectal cancer, or melanoma. Further cancers include, but are not limited to, labia, laryngeal, hypopharyngeal, tongue, salivary gland, stomach, adenocarcinoma, thyroid (medullary and papillary thyroid), kidney, renal parenchymal, cervical, uterine, endometrial, choriocarcinoma, testicular, urinary tract, melanoma, brain tumors, such as glioblastoma, astrocytoma, meningioma, medulloblastoma, and peripheral neuroectodermal tumors, gallbladder cancer, bronchial carcinoma, multiple myeloma, basal cell tumor, teratoma, retinoblastoma, choroidal melanoma, sarcoma, and sarcoma. These include myeloma, rhabdomyosarcoma, craniopharyngeoma, osteosarcoma, chondrosarcoma, myosarcoma, liposarcoma, fibrosarcoma, Ewing's sarcoma, plasmacytoma, non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid leukemia, and gastrointestinal stromal tumor (GIST).

[0199] "Concurrently" or "concurrently," when referring to a method of treatment or therapeutic use, means administration of a compound of formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in combination with one or more second agents, by the same route and at the same time as the compound and the one or more second agents.

[0200] "Individually" or "separately," when referring to a method of treatment or therapeutic use, means a combination of a compound of formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one or more second agents, where the compound and the one or more second agents are administered by different routes and at about the same time.

[0201] The therapeutic administration "over a period of time" refers to the administration of the compound of formula (I), or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer, in combination with one or more second agents, by the same or different routes and at different times. In some embodiments, the administration of the compound or one or more second agents is performed before the start of the administration of the other. In this way, it is possible to administer one of the active ingredients (i.e., the compound of formula (I), or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer, or one or more second agents) for several months, followed by the administration of the other active ingredient or ingredients. In this case, there is no simultaneous administration. Alternative therapeutic administration over a period of time consists of administering two or more active ingredients of the combination over time using different dosing frequencies for each of the active ingredients, such that at some times simultaneous administration of all of the active ingredients occurs while at other times only some of the active ingredients of the combination may be administered (e.g., as an example, a compound of formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one or more second agents, therapeutic administration over a period of time may be such that a compound of formula (I), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, is administered once daily and one or more second agents are administered once every four weeks).

[0202] The compounds may be administered simultaneously (as a single formulation or separate formulations), sequentially, separately, or over a period of time with other drug therapies or treatment modalities. In general, combination therapy contemplates the administration of two or more drugs during a single cycle or course of treatment.

[0203] By "IKZF2-dependent disease or disorder" is meant any disease or disorder that is directly or indirectly affected by modulation of IKZF2 protein levels.

[0204] By "IKZF4-dependent disease or disorder" is meant any disease or disorder that is directly or indirectly affected by modulation of IKZF4 protein levels.

[0205] D. Specific embodiments and methods for testing compounds of formula (I') or formula (I) The present disclosure relates to compounds capable of modulating IKZF2 protein levels, or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof, that are useful for treating diseases and disorders associated with the modulation of IKZF2 protein levels. The present disclosure further relates to compounds or pharma-ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof that are useful for lowering or decreasing IKZF2 protein levels.

[0206] In one embodiment, the compound of formula (I') or formula (I) has formula (Ia): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0207] In another embodiment, the compound of formula (I') or formula (I) has formula (Ib): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0208] In yet another embodiment, the compound of formula (I') or formula (I) has the formula (Ic): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0209] In another embodiment, the compound of formula (I') or formula (I) has the formula (Id): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0210] In another embodiment, the compound of formula (I') or formula (I) has formula (Ie): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0211] In another embodiment, the compound of formula (I') or formula (I) has the formula (If) [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0212] In another embodiment, the compound of formula (I') or formula (I) has formula (Ig): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0213] In another embodiment, the compound of formula (I') or formula (I) has the formula (Ih): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0214] In another embodiment, the compound of formula (I') or formula (I) has the formula (Ii): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0215] In another embodiment, the compound of formula (I') or formula (I) has the formula (Ij): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0216] In another embodiment, the compound of formula (I') or formula (I) has the formula (Ik): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0217] In another embodiment, the compound of formula (I') or formula (I) has the formula (Il) [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0218] In another embodiment, the compound of formula (I') or formula (I) has the formula (Im) [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0219] In another embodiment, the compound of formula (I') or formula (I) has the formula (In [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0220] In another embodiment, the compound of formula (I') or formula (I) has the formula (Io): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0221] In another embodiment, the compound of formula (I') or formula (I) has the formula (Ip): [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0222] In another embodiment, the compound of formula (I') or formula (I) has the formula (Iq) [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0223] In another embodiment, the compound of formula (I') or formula (I) has the formula (Ir) [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0224] In another embodiment, the compound of formula (I') or formula (I) has the formula (Is) [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0225] In another embodiment, the compound of formula (I') or formula (I) has the formula (It [ka] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, and tautomer thereof.

[0226] In some embodiments of the above formulas (e.g., Formula (I), Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie), Formula (If), Formula (Ig), Formula (Ih), Formula (Ii), Formula (Ij), Formula (Ik), Formula (Il), Formula (Im), Formula (In), Formula (Io), Formula (p), Formula (Iq), Formula (Ir), Formula (Is), and Formula (It)), R 1 teeth [ka] In another embodiment, R 1 teeth [ka] It is.

[0227] In some embodiments of the above formula, X 1 is H, (C 1 ~C 3 ) alkyl, (C 1 ~C 6) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, (C 3 ~C 7 ) cycloalkyl, halogen, -CN, -OH, or -NH 2 In another embodiment, X 1 is H, (C 1 ~C 3 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 3 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 In yet another embodiment, X 1 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, (C 3 ~C 7 ) cycloalkyl, or halogen. In another embodiment, X 1 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, or halogen. In yet another embodiment, X 1 is H, halogen, -CN, -OH, or -NH 2 In another embodiment, X 1 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) haloalkyl, halogen, -CN, -OH, or -NH 2 In yet another embodiment, X1 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) haloalkyl, halogen, -OH, or -NH 2 In another embodiment, X 1 is H, (C 1 ~C 4 ) alkyl, halogen, -OH, or -NH 2 In yet another embodiment, X 1 is H, halogen, -OH, or -NH 2 In another embodiment, X 1 is H.

[0228] In some embodiments of the above formula, X 2 is H, (C 1 ~C 3 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, (C 3 ~C 7 ) cycloalkyl, halogen, -CN, -OH, or -NH 2 In another embodiment, X 2 is H, (C 1 ~C 3 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 3 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 In yet another embodiment, X 2 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, (C3 ~C 7 ) cycloalkyl, or halogen. In another embodiment, X 2 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, or halogen. In yet another embodiment, X 2 is H, halogen, -CN, -OH, or -NH 2 In another embodiment, X 2 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) haloalkyl, halogen, -CN, -OH, or -NH 2 In yet another embodiment, X 2 is H, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) haloalkyl, halogen, -OH, or -NH 2 In another embodiment, X 2 is H, (C 1 ~C 4 ) alkyl, halogen, -OH, or -NH 2 In yet another embodiment, X 2 is H, halogen, -OH, or -NH 2 In another embodiment, X 2 is H.

[0229] In some embodiments of the above formula, X 1 is H, and X 2 is (C 1 ~C 3 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, (C3 ~C 7 ) cycloalkyl, halogen, -CN, -OH, or -NH 2 In another embodiment, X 1 is (C 1 ~C 3 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, (C 3 ~C 7 ) cycloalkyl, halogen, -CN, -OH, or -NH 2 and X 2 is H. In yet another embodiment, X 1 is H, and X 2 is H.

[0230] In some embodiments of the above formula, R x is D. In another embodiment, R x is H.

[0231] In some embodiments of the above formula, each R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 3 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 In another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 3 ) haloalkoxy, or halogen. In yet another embodiment, R 2is independently at each occurrence a halogen, -CN, -OH, or -NH 2 In another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) alkoxy, (C 1 ~C 3 ) haloalkyl, or (C 1 ~C 3 ) haloalkoxy. In yet another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, -CN, -OH, or -NH 2 In another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, or -CN. In yet another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, halogen, or -CN. In another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or (C 1 ~C 3 ) haloalkyl. In yet another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or -CN. In another embodiment, R 2 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl. In yet another embodiment, R 2 is independently at each occurrence methyl, ethyl, n-propyl, or isopropyl.

[0232] In some embodiments of the above formula, two R 2along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) form a cycloalkyl or 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) form a cycloalkyl or 5- or 6-membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R 2 along with the carbon atom to which they are attached (C 4 ~C 7 ) form a cycloalkyl or 5- or 6-membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 along with the carbon atom to which they are attached (C 5 ~C 7 ) forming a cycloalkyl or a 5- or 6-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S.

[0233] In another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7) form a cycloalkyl. In another embodiment, two R 2 along with the carbon atom to which they are attached (C 4 ~C 7 ) form a cycloalkyl. In yet another embodiment, two R 2 along with the carbon atom to which they are attached (C 5 ~C 7 ) form a cycloalkyl. In another embodiment, two R 2 together with the carbon atom to which they are attached form a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 together with the carbon atom to which they are attached form a 5-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 together with the carbon atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S.

[0234] In another embodiment, two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 when on adjacent carbon atoms, together form a phenyl or a 5-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S. In yet another embodiment, two R 2 and R , when on adjacent carbon atoms, together form a phenyl or a 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 When on adjacent carbon atoms, they are taken together to form a phenyl. 2 when on adjacent carbon atoms, together form a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 2when on adjacent carbon atoms, together form a 5-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S. In yet another embodiment, two R 2 when on adjacent carbon atoms, together form a 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S.

[0235] In another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R 2 together with the carbon atom to which they are attached form a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 When on adjacent carbon atoms, they are taken together to form a phenyl. 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S.

[0236] In another embodiment, two R 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or two R 2 When two R are on adjacent carbon atoms, they together form a phenyl. 2 along with the carbon atom to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or two R 2 When two R are on adjacent carbon atoms, they together form a phenyl. 2 along with the carbon atom to which they are attached (C 5 ~C 7 ) forming a cycloalkyl or two R 2 when on adjacent carbon atoms, they are taken together to form a phenyl.

[0237] In another embodiment, two R 2 together with the carbon atom to which they are attached form a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, two R 2 together with the carbon atom to which they are attached form a 5-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 2 together with the carbon atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, or two R 2when on adjacent carbon atoms, together form a 5- or 6-membered heteroaryl ring containing 1-3 heteroatoms selected from O, N, and S.

[0238] In some embodiments of the above formula, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 4-6 membered heterocycloalkyl ring optionally substituted with 1-3 substituents each independently selected from haloalkyl, and halogen. In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 4- or 5-membered heterocycloalkyl ring optionally substituted with 1 to 3 substituents each independently selected from haloalkyl, and halogen. In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 3 substituents each independently selected from haloalkyl, and halogen.

[0239] In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C6 ) alkyl, (C 1 ~C 6 ) forms a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from haloalkyl, and halogen. In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S; 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 5- or 6-membered heterocycloalkyl ring substituted with 1 to 4 substituents each independently selected from haloalkyl, haloalkyl, and halogen. In another embodiment, R 2 and R 6 together with the carbon and nitrogen atoms to which they are attached form a 4-6 membered heterocycloalkyl ring, optionally containing 1-2 additional heteroatoms selected from O, N, and S. In another embodiment, R 2 and R 6 together with the carbon and nitrogen atoms to which they are attached form a 4- or 5-membered heterocycloalkyl ring, optionally containing 1-2 additional heteroatoms selected from O, N, and S. In another embodiment, R 2 and R 6 together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring, optionally containing 1-2 additional heteroatoms selected from O, N, and S.

[0240] In some embodiments of the above formula, each R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 3 ) haloalkoxy, halogen, -OH, or -NH 2 In another embodiment, R 3 is (C1 ~C 6 ) alkyl, (C 1 ~C 3 ) alkoxy, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 3 ) haloalkoxy, or halogen. In another embodiment, R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) alkoxy, (C 1 ~C 3 ) haloalkyl, or (C 1 ~C 3 ) haloalkoxy. In another embodiment, R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, or halogen. In another embodiment, R 3 is a halogen, -OH, or -NH 2 In another embodiment, R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, -OH, or -NH 2 In another embodiment, R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, or -OH. In another embodiment, R 3 is (C 1 ~C 6 ) alkyl or (C 1 ~C 3 ) haloalkyl. In another embodiment, R 3 is (C 1 ~C 6 ) alkyl.

[0241] In some embodiments of the above formula, R 4 -OR 5In another embodiment, R 4 -NR 6 R 6’ It is.

[0242] In some embodiments of the above formula, R 5 is H, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 5 is (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0243] In another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 5 is (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0244] In another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, or (C 1 ~C 3 ) haloalkyl, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 5is (C 1 ~C 6 ) alkyl, or (C 1 ~C 3 ) haloalkyl, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 5 is (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S.

[0245] In another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C 3 ~C 7 )cycloalkyl, or a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0246] In another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0247] In another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is (C 6 ~C 10 ) aryl. In yet another embodiment, R 5 is H, (C 1 ~C 3) alkyl, a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 5 is H, (C 1 ~C 3 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three (C 6 ~C 10 ) optionally substituted aryl.

[0248] In some embodiments of the above formula, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each substituted with 1 to 4 R 12 is optionally replaced by

[0249] In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In yet another embodiment, R 6 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 has been replaced with.

[0250] In another embodiment, R 6 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each substituted with 1 to 4 R 12 In yet another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 and cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and the aryl and heteroaryl are optionally substituted with 1 to 4 R 12 is optionally replaced by

[0251] In another embodiment, R 6 is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In yet another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 In yet another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 is optionally replaced by

[0252] In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 2 ~C 6) hydroxyalkyl, a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 and heterocycloalkyl and heteroaryl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 and cycloalkyl and aryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 and cycloalkyl and aryl are optionally substituted with 1 to 4 R 12 is optionally replaced by

[0253] In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7In yet another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 In another embodiment, R 6 is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 is optionally replaced by

[0254] In some embodiments of the above formula, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6’ is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each substituted with 1 to 4 R 12 is optionally replaced by

[0255] In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In yet another embodiment, R 6’ is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 has been replaced with.

[0256] In another embodiment, R 6’ is (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each substituted with 1 to 4 R 12 In yet another embodiment, R 6’ is H, (C 1 ~C6 ) alkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, or a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 and cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and the aryl and heteroaryl are optionally substituted with 1 to 4 R 12 is optionally replaced by

[0257] In another embodiment, R 6’ is (C 1 ~C6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In yet another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 In yet another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 is optionally replaced by

[0258] In another embodiment, R 6’ is H, (C1 ~C 6 ) alkyl, (C 2 ~C 6 ) hydroxyalkyl, a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 and heterocycloalkyl and heteroaryl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 and cycloalkyl and aryl are optionally substituted with 1 to 4 R 12 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 and cycloalkyl and aryl are optionally substituted with 1 to 4 R 12 In yet another embodiment, R 6’ is H or (C 1 ~C 6 ) alkyl, where alkyl is one to three R 7 In another embodiment, R 6’ is H or (C 1 ~C 6) alkyl, where alkyl is one to three R 7 In yet another embodiment, R 6’ is H or (C 1 ~C 6 ) alkyl.

[0259] In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, a 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1 to 3 R 7 In yet another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 In another embodiment, R 6’ is H, (C 1 ~C 6 ) alkyl, (C 3 ~C 7 ) cycloalkyl, or (C 6 ~C 10 ) aryl, where alkyl is one to three R 7 In yet another embodiment, R 6’ is H or (C 1 ~C 6 ) alkyl, where alkyl is one to three R 7 In another embodiment, R 6’ is H or (C 1 ~C 6 ) alkyl, where alkyl is one to three R 7In yet another embodiment, R 6’ is H or (C 1 ~C 6 ) alkyl.

[0260] In some embodiments of the above formula, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R forms a 6-8 membered heterocycloalkyl ring optionally substituted with 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 Forms a 7- or 8-membered heterocycloalkyl ring optionally substituted with

[0261] In another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In another embodiment, R 6 and R 6’optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In yet another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In yet another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 Forms a 5- or 6-membered heterocycloalkyl ring optionally substituted with

[0262] In another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In yet another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In another embodiment, R 6 and R 6’optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In yet another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 In another embodiment, R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 3 R 8 forming a 7-membered heterocycloalkyl ring optionally substituted with

[0263] In some embodiments of the above formula, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2In yet another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from haloalkyl, and halogen. In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S; 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 5- or 6-membered heterocycloalkyl ring substituted with 1 to 4 substituents each independently selected from haloalkyl, haloalkyl, and halogen. 2 and R 6 together with the carbon and nitrogen atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring, optionally containing 1-2 additional heteroatoms selected from O, N, and S.

[0264] In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 5-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from haloalkyl, and halogen. 2 and R 6optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S; 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 5-membered heterocycloalkyl ring substituted with 1 to 4 substituents each independently selected from haloalkyl, haloalkyl, and halogen. In another embodiment, R 2 and R 6 together with the carbon and nitrogen atoms to which they are attached form a 5-membered heterocycloalkyl ring optionally containing 1-2 additional heteroatoms selected from O, N, and S.

[0265] In another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from haloalkyl, and halogen. In yet another embodiment, R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S; 1 ~C 6 ) alkyl, (C 1 ~C 6 ) forms a 6-membered heterocycloalkyl ring substituted with 1 to 4 substituents each independently selected from haloalkyl, and halogen. In another embodiment, R 2 and R 6 together with the carbon and nitrogen atoms to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1-2 additional heteroatoms selected from O, N, and S.

[0266] In some embodiments of the above formula, each R7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 3 R 9 In another embodiment, each R 7 is (C 3 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, where the cycloalkyl and heterocycloalkyl are each selected from 1-3 R 9 In yet another embodiment, each R 7 is (C 6 ~C 10 ) aryl or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where the aryl and heteroaryl are each selected from 1 to 3 R 9 is optionally replaced by

[0267] In another embodiment, each R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one to three R 9 In yet another embodiment, each R 7 is a 4- to 7-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where the heterocycloalkyl and heteroaryl are each independently selected from 1 to 3 R 9 In another embodiment, each R 7 is (C3 ~C 7 ) cycloalkyl or 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl and heteroaryl are each selected from 1 to 3 R 9 In yet another embodiment, each R 7 is a 4- to 7-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, or (C 6 ~C 10 ) aryl, where heterocycloalkyl and aryl are each selected from 1 to 3 R 9 is optionally replaced by

[0268] In another embodiment, each R 7 1 to 3 R 9 Optionally replaced by (C 3 ~C 7 ) cycloalkyl. In yet another embodiment, each R 7 1 to 3 R 9 (C 3 ~C 7 ) cycloalkyl. In another embodiment, each R 7 is (C 3 ~C 7 ) cycloalkyl. In yet another embodiment, each R 7 1 to 3 R 9 Optionally replaced by (C 6 ~C 10 ) aryl. In another embodiment, each R 7 1 to 3 R 9 (C 6 ~C 10 ) aryl. In yet another embodiment, each R 7 is (C 6 ~C 10 ) aryl.

[0269] In another embodiment, each R 7 R is 1 to 3 heteroatoms selected from O, N, and S. 9In yet another embodiment, each R 7 R is 1 to 3 heteroatoms selected from O, N, and S. 9 In another embodiment, each R 7 is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 7 R is 1 to 3 heteroatoms selected from O, N, and S. 9 In another embodiment, each R 7 R is 1 to 3 heteroatoms selected from O, N, and S. 9 In yet another embodiment, each R 7 is a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S.

[0270] In some embodiments of the above formula, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) Haloalkoxy, -CN, -OH, -NR 13 R 14 , -NH 2 , -O(C 3 ~C 7 )cycloalkyl, —O-4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, —O(C 6 ~C 10 ) aryl, or -O-5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkoxy is selected from 1 to 3 R 10cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1 to 3 R 11 In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) Haloalkoxy, -CN, -OH, -NR 13 R 14 , and -NH 2 In another embodiment, each R 8 is independently, for each occurrence, -NR 13 R 14 , -NH 2 , -O(C 3 ~C 7 )cycloalkyl, —O-4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, —O(C 6 ~C 10 ) aryl, or -O-5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) Haloalkoxy, -CN, -OH, -NR 13 R 14 , -O(C 3 ~C 7 )cycloalkyl, —O-4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, —O(C 6 ~C 10) aryl, or -O-5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkoxy is selected from one or two R 10 cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1 to 3 R 11 is optionally replaced by

[0271] In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, -CN, -OH, or -NH 2 where alkoxy is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, -CN, or -OH, where alkoxy is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where alkoxy is (C 3 ~C 7 ) cycloalkyl, 4-7 membered heterocycloalkyl rings containing 1-3 heteroatoms selected from O, N, and S, and (C 6 ~C 10 ) optionally substituted aryl.

[0272] In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where alkoxy is (C 3 ~C 7 ) cycloalkyl, a 4- to 7-membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, and a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where alkoxy is (C 3 ~C 7 ) cycloalkyl, (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where alkoxy is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0273] In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where alkoxy is (C 3 ~C 7) cycloalkyl and a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where alkoxy is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0274] In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4 ) haloalkoxy, halogen, -CN, or -OH, where the alkoxy is optionally substituted with 1 to 3 substituents independently selected from a 4- to 7-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, and a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 8 independently, each occurrence represents a halogen, (C 1 ~C 4 ) alkyl, (C 1 ~C 4 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 4) haloalkoxy, halogen, -CN, or -OH, where alkoxy is (C 3 ~C 7 ) cycloalkyl and (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl.

[0275] In another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, -CN, -OH, or -NH 2 In another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -CN, -OH, or -NH 2 In yet another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, or halogen. In another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, or -OH. In yet another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, or -NH 2 In another embodiment, each R 8 is independently at each occurrence a halogen, -CN, -OH, or -NH 2 In yet another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or halogen. In another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl or halogen. In another embodiment, each R 8 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, halogen, or -CN. In yet another embodiment, each R 8 is independently at each occurrence halogen or -CN. 8 is independently at each occurrence a halogen.

[0276] In some embodiments of the above formula, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 6 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 5 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 6) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 5 ) a cycloalkyl or a 6-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 5 ) forming a cycloalkyl or a 4-5 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0277] In another embodiment, two R 8 along with the atoms to which they are attached (C 5 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 along with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 along with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl. In yet another embodiment, two R 8 along with the atoms to which they are attached (C 5 ~C 6 ) form a cycloalkyl. In another embodiment, two R 8 along with the atoms to which they are attached (C 6 ~C 7 ) form a cycloalkyl. In yet another embodiment, two R 8 along with the atoms to which they are attached (C 5) form a cycloalkyl. In another embodiment, two R 8 along with the atoms to which they are attached (C 6 ) form a cycloalkyl. In yet another embodiment, two R 8 along with the atoms to which they are attached (C 7 ) forming a cycloalkyl.

[0278] In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 7 ) form a cycloalkyl. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 5 ~C 7 ) form a cycloalkyl. In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 5 ~C 6 ) form a cycloalkyl. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 6 ~C 7 ) form a cycloalkyl. In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 5 ) form a cycloalkyl. In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 6 ) form a cycloalkyl. In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 7 ) forming a cycloalkyl.

[0279] In another embodiment, two R 8 together with the atom to which they are attached form a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R 8 together with the atom to which they are attached form a 4- or 5-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 together with the atom to which they are attached form a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R 8 together with the atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 together with the atom to which they are attached form a 6- or 7-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R 8 together with the atom to which they are attached form a 5-membered heterocycloalkyl ring containing 1 to 2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 together with the atom to which they are attached form a 6-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R 8 together with the atom to which they are attached form a 7-membered heterocycloalkyl ring containing 1 to 2 heteroatoms selected from O, N, and S.

[0280] In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 In another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 In yet another embodiment, two R 8 are two R's along with the atoms to which they are attached. 15 Forms a 7-membered heterocycloalkyl ring containing 1 to 2 heteroatoms selected from O, N, and S, optionally substituted with

[0281] In another embodiment, two R 8 are on the same carbon atom, two R 15 Optionally replaced by (C 4 ~C 7) forms a spirocycloalkyl or 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 8 If they are on adjacent atoms, they are combined with the atom to which they are attached to form two R 15 Optionally replaced by (C 4 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0282] In another embodiment, two R 8 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 8 When on adjacent atoms, together with the atom to which they are attached, they form a phenyl or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 8 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl. In another embodiment, two R 8 When on adjacent atoms, together with the atom to which they are attached, form a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 8 when on adjacent atoms, together with the atom to which they are attached form a phenyl.

[0283] In another embodiment, two R 8 together with the same atom to which they are attached form =(O).

[0284] In some embodiments of the above formula, each R 9 are independently calculated for each occurrence, (C 1 ~C 6) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, (C 3 ~C 6 ) Cycloalkyl, -OH, -CN, -NH 2 , or -NR 13 R 14 In another embodiment, R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, (C 3 ~C 6 ) cycloalkyl, -OH, -CN, or NR 13 R 14 In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, or -NH 2 In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, or -CN. In another embodiment, each R9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, halogen, or -CN. In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, or -CN. In yet another embodiment, each R 9 is independently at each occurrence a halogen, -OH, -CN, or -NH 2 In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, or halogen. In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, or halogen. In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or halogen. In yet another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or -CN. In another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C3 ) alkyl or (C 1 ~C 3 ) haloalkyl. In yet another embodiment, each R 9 is independently at each occurrence halogen or -CN. 9 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or halogen. In yet another embodiment, each R 9 are independently calculated for each occurrence, (C 1 ~C 3 ) haloalkyl.

[0285] In some embodiments of the above formula, two R 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 4 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 5 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6) optionally substituted with 1 to 3 substituents each independently selected from haloalkyl, halogen, and -CN (C 5 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 are optionally substituted with 1 to 3 halogens together with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In yet another embodiment, two R 9 along with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl. In another embodiment, two R 9 along with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl. In another embodiment, two R 9 along with the atoms to which they are attached (C 5 ~C 6 ) form a cycloalkyl. In yet another embodiment, two R 9 along with the atoms to which they are attached (C 6 ~C 7 ) form a cycloalkyl. In another embodiment, two R 9 along with the atoms to which they are attached (C 4 ) form a cycloalkyl. In another embodiment, two R 9 along with the atoms to which they are attached (C 5 ) form a cycloalkyl. In yet another embodiment, two R 9 along with the atoms to which they are attached (C 6) form a cycloalkyl. In another embodiment, two R 9 along with the atoms to which they are attached (C 7 ) forming a cycloalkyl.

[0286] In another embodiment, two R 9 together with the atom to which they are attached form a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 together with the atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 together with the atom to which they are attached form a 6- or 7-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 together with the atom to which they are attached form a 5-membered heterocycloalkyl ring containing 1 to 2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 together with the atom to which they are attached form a 6-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 9 together with the atom to which they are attached form a 7-membered heterocycloalkyl ring containing 1 to 2 heteroatoms selected from O, N, and S.

[0287] In another embodiment, two R 9 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 9 When on adjacent atoms, together with the atom to which they are attached, they form a phenyl or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 9on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl or a 5-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 9 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl or a 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 9 when on adjacent atoms, together with the atom to which they are attached form a phenyl or a 5-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S.

[0288] In another embodiment, two R 9 When on adjacent atoms, together with the atom to which they are attached, they form a phenyl or a 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 9 When on adjacent atoms, they form, together with the atom to which they are attached, a phenyl. 9 When on adjacent atoms, together with the atom to which they are attached, form a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, two R 9 When on adjacent atoms, together with the atom to which they are attached, form a 5-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 9 when on adjacent atoms, together with the atom to which they are attached form a 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S.

[0289] In some embodiments of the above formula, each R 10 is (C 3 ~C 7) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 is (C 3 ~C 7 ) cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 10 is (C 6 ~C 10 ) aryl or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S.

[0290] In another embodiment, each R 10 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl. In yet another embodiment, each R 10 is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 is (C 3 ~C 7 ) cycloalkyl or 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 10 is a 4-7 membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, or (C 6 ~C 10 ) aryl. In yet another embodiment, each R 10 is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, each R 10is a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 is (C 3 ~C 7 ) cycloalkyl. In yet another embodiment, each R 10 is (C 6 ~C 10 ) aryl.

[0291] In some embodiments of the above formula, each R 11 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, or -NH 2 In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, or -CN. In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, halogen, or -CN. In another embodiment, each R 11 are independently calculated for each occurrence, (C1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, or -CN. In yet another embodiment, each R 11 is independently at each occurrence a halogen, -OH, -CN, or -NH 2 In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, or halogen. In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, or halogen. In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or halogen. In yet another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or -CN. In another embodiment, each R 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or (C 1 ~C 3 ) haloalkyl. In yet another embodiment, each R 11 is independently at each occurrence halogen or -CN. 11 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or halogen.

[0292] In some embodiments of the above formula, each R 12 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, or -NH 2 In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, or -CN. In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, halogen, or -CN. In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, halogen, or -CN. In yet another embodiment, each R 12 is independently at each occurrence a halogen, -OH, -CN, or -NH 2 In another embodiment, each R 12are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, or halogen. In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, (C 1 ~C 6 ) alkoxy, or halogen. In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or halogen. In yet another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl, (C 1 ~C 3 ) haloalkyl, or -CN. In another embodiment, each R 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or (C 1 ~C 3 ) haloalkyl. In yet another embodiment, each R 12 is independently at each occurrence halogen or -CN. 12 are independently calculated for each occurrence, (C 1 ~C 3 ) alkyl or halogen.

[0293] In some embodiments of the above formula, two R 12 along with the atoms to which they are attached (C 4 ~C 7) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 5 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 6 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 6 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 5 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0294] In some embodiments of the above formula, two R 12 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl or 6- or 7-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 7) form a cycloalkyl or 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or a 4- or 5-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0295] In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl. In another embodiment, two R 12 along with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl. In another embodiment, two R 12 along with the atoms to which they are attached (C 6 ~C 7 ) form a cycloalkyl. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 6 ) form a cycloalkyl. In another embodiment, two R 12 along with the atoms to which they are attached (C 4 ~C 5 ) forming a cycloalkyl.

[0296] In another embodiment, two R 12 together with the atom to which they are attached form a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 together with the atom to which they are attached form a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 together with the atom to which they are attached form a 6- or 7-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12together with the atom to which they are attached form a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 12 together with the atom to which they are attached form a 4- or 5-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0297] In some embodiments of the above formula, R 13 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 13 is (C 1 ~C 6 ) alkyl and (C 1 ~C 6 ) haloalkyl. In another embodiment, R 13 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 13 is (C 3 ~C 7 ) cycloalkyl and a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 13 is (C 6 ~C 10) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0298] In another embodiment, R 13 is (C 3 ~C 7 ) cycloalkyl and (C 6 ~C 10 ) aryl. In yet another embodiment, R 13 is selected from 4-7 membered heterocycloalkyl rings containing 1-3 heteroatoms selected from O, N, and S, and 5- or 6-membered heteroaryls containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 13 is (C 3 ~C 7 ) cycloalkyl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 13 is a 4- to 7-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, and (C 6 ~C 10 ) aryl. In yet another embodiment, R 13 is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 13 is a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 13 is (C 3 ~C 7 ) cycloalkyl. In yet another embodiment, each R 13 is (C 6 ~C 10 ) aryl.

[0299] In some embodiments of the above formula, R 14 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 14 is (C 1 ~C 6 ) alkyl and (C 1 ~C 6 ) haloalkyl. In another embodiment, R 14 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 14 is (C 3 ~C 7 ) cycloalkyl and a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 14 is (C 6 ~C 10 ) aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S.

[0300] In another embodiment, R 14 is (C 3 ~C 7 ) cycloalkyl and (C 6 ~C 10 ) aryl. In yet another embodiment, R 14 is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, and a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 14 is (C 3 ~C 7) cycloalkyl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 14 is a 4- to 7-membered heterocycloalkyl ring containing 1 to 3 heteroatoms selected from O, N, and S, and (C 6 ~C 10 ) aryl. In yet another embodiment, R 14 is a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 14 is a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S. In another embodiment, R 14 is (C 3 ~C 7 ) cycloalkyl. In yet another embodiment, R 14 is (C 6 ~C 10 ) aryl.

[0301] In some embodiments of the above formula, two R 15 along with the atoms to which they are attached (C 4 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 5 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 6 ~C 7 ) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 6) a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 5 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0302] In some embodiments of the above formula, two R 15 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl or 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl or 6- or 7-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl or 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or a 4- or 5-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0303] In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 7 ) form a cycloalkyl. In another embodiment, two R 15 along with the atoms to which they are attached (C 5 ~C 7 ) form a cycloalkyl. In another embodiment, two R 15along with the atoms to which they are attached (C 6 ~C 7 ) form a cycloalkyl. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 6 ) form a cycloalkyl. In another embodiment, two R 15 along with the atoms to which they are attached (C 4 ~C 5 ) forming a cycloalkyl.

[0304] In another embodiment, two R 15 together with the atom to which they are attached form a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 together with the atom to which they are attached form a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 together with the atom to which they are attached form a 6- or 7-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 together with the atom to which they are attached form a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S. In another embodiment, two R 15 together with the atom to which they are attached form a 4- or 5-membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0305] In some embodiments of the above formula, m is 0, 1, or 2. In other embodiments, m is 0 or 1. In yet other embodiments, m is 1 or 2. In other embodiments, m is 0. In yet other embodiments, m is 1. In other embodiments, m is 2.

[0306] In some embodiments of the above formula, m1 is 0, 1, or 2. In other embodiments, m1 is 0 or 1. In yet other embodiments, m1 is 1 or 2. In other embodiments, m1 is 0. In yet other embodiments, m1 is 1. In other embodiments, m1 is 2.

[0307] In some embodiments of the above formula, n1 is 0, 1, or 2. In other embodiments, n1 is 1, 2, or 3. In other embodiments, n1 is 0 or 1. In other embodiments, n1 is 1 or 2. In other embodiments, n1 is 2 or 3. In other embodiments, n1 is 0. In other embodiments, n1 is 1. In other embodiments, n1 is 2. In other embodiments, n1 is 3.

[0308] In some embodiments of the above formula, each s and n is independently 1, 2, or 3, where s+n is ≦4. In another embodiment, each s and n is independently 1 or 2, where s+n is ≦4. In another embodiment, each s and n is independently 2 or 3, where 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.

[0309] In some embodiments of the above formula, R 1 teeth [ka] and R 4 -OR 5 It is.

[0310] In some embodiments of the above formula, R 1 teeth [ka] and R 4 -NR 6 R 6’ It is.

[0311] In some embodiments of the above formula, R 1 teeth [ka] and n1 is 1 or 2.

[0312] In some embodiments of the above formula, R 1 teeth [ka] n1 is 1 or 2, and R 4 -OR 5 It is.

[0313] In some embodiments of the above formula, R 1 teeth [ka] n1 is 1 or 2, and R 4 -NR 6 R 6’ It is.

[0314] In some embodiments of the above formula, n1 is 1 or 2, and R 4 -OR 5 It is.

[0315] In some embodiments of the above formula, n1 is 1 or 2, and R 4 -NR 6 R 6’ It is.

[0316] In some embodiments of the above formula, R 1 teeth [ka] where n1 is 1 or 2, and m1 is 0.

[0317] In some embodiments of the above formula, R 1 teeth [ka] where n1 is 1 or 2, m1 is 0, and R 4 -OR 5 It is.

[0318] In some embodiments of the above formula, R 1 teeth [ka] where n1 is 1 or 2, m1 is 0, and R 4 -NR 6 R 6’ It is.

[0319] In some embodiments of the above formula, m1 is 0 and R 4 -NR 6 R 6’ It is.

[0320] In some embodiments of the above formula, m1 is 0 and R 4 -OR 5 It is.

[0321] In some embodiments of the above formula, R 1 teeth [ka] and m1 is 0.

[0322] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 It is.

[0323] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ It is.

[0324] In some embodiments of the above formula, n1 is 1 or 2 and m1 is 0.

[0325] In some embodiments of the above formula, n1 is 1 or 2, m1 is 0, and R 4 -OR 5 It is.

[0326] In some embodiments of the above formula, n1 is 1 or 2, m1 is 0, and R 4 -NR 6 R 6’ It is.

[0327] In some embodiments of the above formula, R 1 teeth [ka] where n1 is 1 or 2, and m1 is 2.

[0328] In some embodiments of the above formula, R 1 teeth [ka] where n1 is 1 or 2, m1 is 2, and R 4 -OR5 It is.

[0329] In some embodiments of the above formula, R 1 teeth [ka] where n1 is 1 or 2, m1 is 2, and R 4 -NR 6 R 6’ It is.

[0330] In some embodiments of the above formula, R 1 teeth [ka] and m1 is 2.

[0331] In some embodiments of the above formula, R 1 teeth [ka] m1 is 2, and R 4 -OR 5 It is.

[0332] In some embodiments of the above formula, R 1 teeth [ka] m1 is 2, and R 4 -NR 6 R 6’ It is.

[0333] In some embodiments of the above formula, n1 is 1 or 2 and m1 is 2.

[0334] In some embodiments of the above formula, n1 is 1 or 2, m1 is 2, and R 4 -OR5 It is.

[0335] In some embodiments of the above formula, n1 is 1 or 2, m1 is 2, and R 4 -NR 6 R 6’ It is.

[0336] In some embodiments of the above formula, m1 is 2 and R 4 -OR 5 It is.

[0337] In some embodiments of the above formula, m1 is 2 and R 4 -NR 6 R 6’ It is.

[0338] In some embodiments of the above formula, R 1 teeth [ka] where n is 2 and s is 1 or 2.

[0339] In some embodiments of the above formula, R 1 teeth [ka] and R 4 -OR 5 It is.

[0340] In some embodiments of the above formula, R 1 teeth [ka] and R 4 -NR 6 R 6’ It is.

[0341] In some embodiments of the above formula, R 1teeth [ka] where n is 2, s is 1 or 2, and m is 0 or 1.

[0342] In some embodiments of the above formula, R 1 teeth [ka] where n is 2, s is 1 or 2, m is 0 or 1, and R 4 -OR 5 It is.

[0343] In some embodiments of the above formula, R 1 teeth [ka] where n is 2, s is 1 or 2, m is 0 or 1, and R 4 -NR 6 R 6’ It is.

[0344] In some embodiments of the above formula, R 1 teeth [ka] where n is 2, s is 1 or 2, m is 0 or 1, and R 4 -OR 5 It is.

[0345] In some embodiments of the above formula, R 1 teeth [ka] where n is 2, s is 1 or 2, m is 0 or 1, and R 4 -NR6 R 6’ It is.

[0346] In some embodiments of the above formula, R 1 teeth [ka] and m is 0 or 1.

[0347] In some embodiments of the above formula, R 1 teeth [ka] m is 0 or 1, and R 4 -OR 5 It is.

[0348] In some embodiments of the above formula, R 1 teeth [ka] m is 0 or 1, and R 4 -NR 6 R 6’ It is.

[0349] In some embodiments of the above formula, R 1 teeth [ka] m is 0 or 1, and R 4 -OR 5 It is.

[0350] In some embodiments of the above formula, R 1 teeth [ka] m is 0 or 1, and R 4-NR 6 R 6’ It is.

[0351] In some embodiments of the above formula, n is 2, s is 1 or 2, and m is 0 or 1.

[0352] In some embodiments of the above formula, n is 2, s is 1 or 2, m is 0 or 1, and R 4 -OR 5 It is.

[0353] In some embodiments of the above formula, n is 2, s is 1 or 2, m is 0 or 1, and R 4 -NR 6 R 6’ It is.

[0354] In some embodiments of the above formula, n is 2, s is 1 or 2, and R 4 -OR 5 It is.

[0355] In some embodiments of the above formula, n is 2, s is 1 or 2, and R 4 -NR 6 R 6’ It is.

[0356] In some embodiments of the above formula, m is 0 or 1, and R 4 -OR 5 It is.

[0357] In some embodiments of the above formula, m is 0 or 1, and R 4 -NR 6 R 6’ It is.

[0358] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl.

[0359] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 0. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10)aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 2.

[0360] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 0. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl, and n1 is 2.

[0361] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 substituents, H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl.

[0362] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 substituents, H or (C 1 ~C 6 ) alkyl, and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 substituents, H or (C 1 ~C 6 ) alkyl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 substituents, H or (C 1 ~C 6 ) alkyl, and n1 is 0. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 substituents, H or (C 1 ~C 6 ) alkyl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 is (C 6 ~C 10 )aryl and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 substituents, H or (C 1 ~C 6 ) alkyl, and n1 is 2.

[0363] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl, and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl, and n1 is 0. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl, and n1 is 2.

[0364] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0365] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 and n1 is 0. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8and n1 is 2.

[0366] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 and R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0367] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 0.

[0368] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 2.

[0369] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 and R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0370] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 0, 1, or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R8 R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 0.

[0371] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 2.

[0372] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 and R 7 is (C 6 ~C 10 ) aryl.

[0373] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 (C 6 ~C 10 ) aryl, and n1 is 0, 1, or 2.

[0374] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 (C 6 ~C 10 ) aryl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 (C 6 ~C 10 ) aryl, and n1 is 0.

[0375] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8R 7 (C 6 ~C 10 ) aryl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, or (C 1 ~C 6 ) haloalkyl, where alkyl is one to three R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 R 7 (C 6 ~C 10 ) aryl, and n1 is 2.

[0376] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl. In another embodiment, R1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, and R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl.

[0377] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, and R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0378] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 0, 1, or 2.

[0379] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 0.

[0380] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 2.

[0381] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, and R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0382] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 0, 1, or 2.

[0383] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 0.

[0384] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 2.

[0385] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, and R 7 is (C 6 ~C 10 ) aryl. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 (C 6 ~C 10 ) aryl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 (C 6 ~C 10 ) aryl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 H, optionally substituted with (C 1 ~C 6 ) haloalkyl, or (C 1 ~C 6 ) alkyl, R 7 (C 6 ~C 10 ) aryl, and n1 is 2.

[0386] In some embodiments of the above formula, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0387] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 and n1 is 2.

[0388] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0389] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is one or two R 9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 is one or two R9 Optionally replaced by (C 6 ~C 10 ) aryl, and n1 is 2.

[0390] In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 6 ~C 10 ) aryl. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 (C 6 ~C 10 ) aryl, and n1 is 1 or 2. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 (C 6 ~C 10 ) aryl, and n1 is 1. In another embodiment, R 1 teeth [ka] m1 is 0, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 7 (C 6 ~C 10 ) aryl, and n1 is 2.

[0391] In some embodiments of the above formula, R 1 teeth [ka] wherein m is 0, n is 1, and s is 1. In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -OR 5 In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) optionally substituted with aryl, H, (C 6 ~C 10 ) aryl, or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl.

[0392] In some embodiments of the above formula, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -NR 6 R 6’ In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 3~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0393] In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is one or more R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0394] In another embodiment, R 1 teeth [ka] m is 0, n is 1, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C6 ) alkyl, and R 7 is (C 6 ~C 10 ) aryl.

[0395] In some embodiments of the above formula, R 1 teeth [ka] wherein m is 0, n is 2, and s is 1. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -OR 5 In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl.

[0396] In some embodiments of the above formula, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -NR 6 R 6’ In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 3 ~C 7 ) cycloalkyl or (C6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0397] In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is one or more R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0398] In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R7 is (C 6 ~C 10 ) aryl.

[0399] In some embodiments of the above formula, R 1 teeth [ka] wherein m is 0, n is 2, and s is 2. In another embodiment, R 1 teeth [ka] where n is 2, s is 2, and R 4 -OR 5 In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl.

[0400] In some embodiments of the above formula, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -NR 6 R 6’ In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0401] In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is one or more R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0402] In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 2, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 6 ~C10 ) aryl.

[0403] In some embodiments of the above formula, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, and R 4 -OR 5 In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, R 4 -OR 5 and R 5 1 to 3 (C 6 ~C 10 ) aryl, H or (C 1 ~C 6 ) alkyl.

[0404] In some embodiments of the above formula, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, and R 4 -NR 6 R 6’ In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl. In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 3 ~C 7 ) cycloalkyl or (C 6 ~C 10 ) aryl, where cycloalkyl and aryl are each independently one or two R 9 is optionally replaced by

[0405] In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is one or more R 9 Optionally replaced by (C 6 ~C 10 ) aryl.

[0406] In another embodiment, R 1 teeth [ka] m is 0, n is 2, s is 1 or 2, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, and R 7 is (C 6 ~C 10 ) aryl.

[0407] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 1, 2, or 3, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 2 or 3, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0408] In another embodiment, R1 teeth [ka] m1 is 0, n1 is 1 or 2, R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0409] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 1, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0410] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 2, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0411] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 3, and R 4 -NR 6 R 6’ and R 6 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl, R 6’ 1 to 3 R 7 Optionally substituted with H or (C 1 ~C 6 ) alkyl or R6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0412] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 1, 2, or 3, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In yet another embodiment, R 1 teeth [ka] m1 is 0, n1 is 2 or 3, R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0413] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 1 or 2, R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In yet another embodiment, R 1 teeth [ka] m1 is 0, n1 is 1, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0414] In another embodiment, R 1 teeth [ka] m1 is 0, n1 is 2, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 In yet another embodiment, R 1 teeth [ka] m1 is 0, n1 is 3, and R 4 -NR 6 R 6’ and R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forms a 4- to 7-membered heterocycloalkyl ring optionally substituted with

[0415] Embodiment 1: A compound of formula (I') X 1 and X 2 are independently H, (C 1 ~C 4 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 4 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, (C 3 ~C 7 ) cycloalkyl, halogen, -CN, -OH, or -NH 2 and R x is H or D, R 1 teeth, [ka] and Each R 2 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 or The Two R's 2 along with the carbon atom to which they are attached (C3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S; or R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, or -NH 2 and R 4 -OR 5 or -NR 6 R 6’ and R 5 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10)aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 2 ~C 6 ) hydroxyalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 and cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 4 R 12 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forming a 4-8 membered heterocycloalkyl ring optionally substituted with R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 4 R 9 and optionally replaced by Each R 8 independently, each occurrence represents a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) Haloalkoxy, -CN, -OH, -NR 13 R 14 , -NH 2 , -O(C 3 ~C 7 )cycloalkyl, —O-4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, —O(C 6 ~C 10 ) aryl, or -O-5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkoxy is selected from 1 to 3 R 10 cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1 to 3 R 11 or The Two R's 8 are two R's along with the atoms to which they are attached. 15 Optionally replaced by (C 4 ~C 7) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, or two R 8 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, or two R 8 form =(O) with the same atom to which they are attached, Each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, or -NH 2 or The Two R's 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 4 ~C 7 ) a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, or two R 9 on adjacent atoms, together with the atoms to which they are attached, (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; Each R 10 are independently calculated for each occurrence, (C 3 ~C 7) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; Each R 11 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, and -NH 2 is selected from Each R 12 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, -CN, or -NH 2 and The Two R's 12 along with the atoms to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; R 13 and R 14 are each independently: (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10) aryl, and 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S; The Two R's 15 along with the atoms to which they are attached (C 4 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 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, where s+n is ≦4; or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0416] Embodiment 2. The compound of embodiment 1 having the formula (I), R x is H or D, R 1 teeth [ka] and Each R 2 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 or The Two R's 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S; or R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, OH, or -NH 2 and R 4 -OR 5 or -NR 6 R 6’ and R 5 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10) optionally substituted with 1 to 3 substituents independently selected from aryl and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; R 6 and R 6’ are independently H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forming a 4- to 7-membered heterocycloalkyl ring optionally substituted with R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 4 R 9 and optionally replaced by Each R 8 independently, each occurrence represents a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, -CN, -OH, or -NH 2 where alkoxy is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl, and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; The Two R's 8 along with the atoms to which they are attached (C 5 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; Each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 or The Two R's 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2(C 5 ~C 7 ) forming a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 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, where s+n is ≦4. or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0417] Embodiment 2A. The compound of embodiment 1 having formula (I), R x is H or D, R 1 teeth [ka] and Each R 2 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -CN, -OH, or -NH 2 or The Two R's 2 along with the carbon atom to which they are attached (C 3 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S, or two R 2 when on adjacent carbon atoms, together form a phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from O, N, and S; or R2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 3 is (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) alkoxy, (C 1 ~C 6 ) haloalkyl, (C 1 ~C 6 ) haloalkoxy, halogen, -OH, or -NH 2 and R 4 -OR 5 or -NR 6 R 6’ and R 5 is H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 )aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where alkyl is (C 6 ~C 10 ) optionally substituted with 1 to 3 substituents independently selected from aryl and 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S; R 6 and R 6’are independently H, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, (C 3 ~C 7 ) cycloalkyl, 5- or 6-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where the alkyl is selected from 1-3 R 7 or R 6 and R 6’ optionally contain, together with the nitrogen atom to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and 1 to 4 R 8 forming a 4- to 7-membered heterocycloalkyl ring optionally substituted with R 2 and R 6 optionally contain, together with the carbon and nitrogen atoms to which they are attached, 1 to 2 additional heteroatoms selected from O, N, and S, and (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 forming a 5- or 6-membered heterocycloalkyl ring optionally substituted with 1 to 4 substituents each independently selected from Each R 7 is (C 3 ~C 7 ) cycloalkyl, a 4-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from O, N, and S; (C 6 ~C 10 ) aryl, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, where cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently selected from 1 to 4 R 9 and optionally replaced by Each R 8 independently, each occurrence represents a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -CN, -OH, or -NH 2 or The Two R's 8 along with the atoms to which they are attached (C 5 ~C 7 ) forming a cycloalkyl or a 4-7 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; Each R 9 are independently calculated for each occurrence, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) haloalkyl, halogen, -OH, -CN, or -NH 2 or The Two R's 9 along with the atoms to which they are attached (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Haloalkyl, halogen, -OH, -CN, and -NH 2 (C 5 ~C 7 ) forming a cycloalkyl or a 5-7 membered heterocycloalkyl ring containing 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, where s+n is ≦4. or pharma- ceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0418] Embodiment 3.R 1 but, [ka] The compound of any one of embodiments 1, 2, and 2A, wherein

[0419] Embodiment 4. The compound of any one of embodiments 1, 2, and 2A, wherein n1 is 0, 1, or 2.

[0420] Embodiment 5. The compound of any one of embodiments 1-3 and 2A, wherein m1 is 0.

[0421] Embodiment 6. The compound of any one of embodiments 1-3 and 2A, wherein m1 is 2.

[0422] Embodiment 7.R 1 but [ka] The compound of any one of embodiments 1, 2, and 2A, wherein

[0423] Embodiment 8. The compound of embodiment 7, wherein n is 2 and s is 1 or 2.

[0424] Embodiment 9. A compound of embodiment 7 or 8, wherein m is 0 or 1.

[0425] Embodiment 10. A compound of any one of embodiments 1, 2, and 2A having formula (Ia) or formula (Ib), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0426] Embodiment 11. The compound of any one of embodiments 1, 2, and 2A having Formula (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), or (Ij), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0427] Embodiment 12. The compound of any one of embodiments 1, 2, and 2A having the formula (Ik), (Il), (Im), (In), (Io), or (Ip), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0428] Embodiment 13.R 4 -OR 5 The compound of any one of embodiments 1-12 and 2A, wherein

[0429] Embodiment 14.R 4 Ga-NR 6 R 6’ The compound of any one of embodiments 1-12 and 2A, wherein

[0430] Embodiment 15. A compound of any one of embodiments 1, 2, and 2A having formula (Iq), (Ir), (Is), or (It), or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0431] EMBODIMENT 16.

[0432] [Table 1]

[0433] [Table 2]

[0434] [Table 3]

[0435] [Table 4]

[0436] [Table 5]

[0437]

Table 6

[0438]

Table 7

[0439]

Table 8

[0440]

Table 9

[0441]

Table 10

[0442]

Table 11

[0443]

Table 12

[0444]

Table 13

[0445]

Table 14

[0446]

Table 15

[0447]

Table 16

[0448]

Table 17

[0449]

Table 18

[0450]

Table 19

[0451]

Table 20

[0452]

Table 21

[0453]

Table 22

[0454]

Table 23

[0455]

Table 24

[0456]

Table 25

[0457]

Table 26

[0458]

Table 27

[0459]

Table 28

[0460]

Table 29

[0461]

Table 30

[0462]

Table 31

[0463]

Table 32

[0464]

Table 33

[0465]

Table 34

[0466]

Table 35

[0467]

Table 36

[0468]

Table 37

[0469]

Table 38

[0470]

Table 39

[0471]

Table 40

[0472]

Table 41

[0473]

Table 42

[0474]

Table 43

[0475]

Table 44

[0476]

Table 45

[0477]

Table 46

[0478]

Table 47

[0479]

Table 48

[0480]

Table 49

[0481]

Table 50

[0482]

Table 51

[0483]

Table 52

[0484]

Table 53

[0485]

Table 54

[0486]

Table 55

[0487]

Table 56

[0488]

Table 57

[0489]

Table 58

[0490]

Table 59

[0491]

Table 60

[0492]

Table 61

[0493]

Table 62

[0494]

Table 63

[0495]

Table 64

[0496]

Table 65

[0497]

Table 66

[0498]

Table 67

[0499]

Table 68

[0500]

Table 69

[0501]

Table 70

[0502]

Table 71

[0503]

Table 72

[0504]

Table 73

[0505]

Table 74

[0506]

Table 75

[0507]

Table 76

[0508]

Table 77

[0509]

Table 78

[0510]

Table 79

[0511]

Table 80

[0512]

Table 81

[0513]

Table 82

[0514]

Table 83

[0515]

Table 84

[0516]

Table 85

[0517]

Table 86

[0518]

Table 87

[0519]

Table 88

[0520] [Table 89]

[0521] [Table 90] or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0522] Embodiment 17. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of embodiments 1-16 and 2A, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier or excipient.

[0523] Embodiment 18. The pharmaceutical composition of embodiment 17, further comprising at least one additional pharmaceutical agent.

[0524] Embodiment 19. A pharmaceutical composition of embodiment 17 or embodiment 18 for use in the treatment of a disease or disorder affected by reduced IKZF2 protein levels.

[0525] Embodiment 20. A method of degrading IKZF2 comprising administering to a patient in need thereof a compound of any one of embodiments 1-16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0526] Embodiment 21. A method of treating a disease or disorder affected by modulation of IKZF2 protein levels comprising administering to a patient in need thereof a compound of any one of embodiments 1-16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0527] Embodiment 22. A method of modulating IKZF2 protein levels comprising administering to a patient in need thereof a compound of any one of embodiments 1-16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0528] Embodiment 23. A method of reducing proliferation of a cell, comprising contacting a cell with a compound of any one of embodiments 1-16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and reducing IKZF2 protein levels.

[0529] Embodiment 24. A method of treating cancer comprising administering to a patient in need thereof a compound of any one of embodiments 1-15 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0530] Embodiment 25. The method of embodiment 24, wherein the cancer is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, and Ewing's sarcoma.

[0531] Embodiment 26 The method of embodiment 24, wherein the cancer is an immune response-deficient cancer or an immunogenic cancer.

[0532] Embodiment 27. A method for reducing IKZF2 protein levels in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to any one of embodiments 1-16 and 2A, or a pharma- ceutically acceptable salt.

[0533] The method of any one of embodiments 28.20 to 27, wherein administration is orally, parentally, subcutaneously, by injection or infusion.

[0534] Embodiment 29. A compound according to any one of embodiments 1 to 16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in treating a disease or disorder affected by reduced IKZF2 protein levels.

[0535] Embodiment 30. Use of a compound according to any one of embodiments 1 to 16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for the treatment of a disease or disorder affected by reduced IKZF2 protein levels.

[0536] Embodiment 31. A compound according to any one of embodiments 1 to 16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in the manufacture of a medicament for the treatment of a disease or disorder associated with decreased IKZF2 protein levels.

[0537] Embodiment 32. The compound of embodiment 31, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, and Ewing's sarcoma.

[0538] Embodiment 33. Use of a compound according to any one of embodiments 1 to 16 and 2A, or a pharma- ceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the treatment of a disease or disorder associated with decreased IKZF2 protein levels.

[0539] Embodiment 34. The use of embodiment 33, wherein the disease or disorder is selected from prostate cancer, breast cancer, lymphoma, leukemia, myeloma, bladder cancer, 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, bile duct cancer, gastric cancer, and soft tissue sarcomas selected from rhabdomyosarcoma (RMS), synovial sarcoma, osteosarcoma, rhabdoid carcinoma, and Ewing's sarcoma.

[0540] Embodiment 35. The method of embodiment 24, wherein the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid leukemia, and gastrointestinal stromal tumor (GIST).

[0541] Embodiment 36. The compound of embodiment 31, wherein the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid leukemia, and gastrointestinal stromal tumor (GIST).

[0542] Embodiment 37. The use of embodiment 33, wherein the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid leukemia, and gastrointestinal stromal tumor (GIST).

[0543] In another embodiment of the present disclosure, the compounds of the present disclosure are enantiomers. In some embodiments, the compounds are (S)-enantiomers. In other embodiments, the compounds are (R)-enantiomers. In yet other embodiments, the compounds of the present disclosure can be (+) or (-) enantiomers.

[0544] It is to be understood that all isomers, including mixtures thereof, are included within the present disclosure. When a compound contains a double bond, the substituent can be in the E or Z configuration. When a compound contains a disubstituted cycloalkyl, the cycloalkyl substituent can have a cis or trans configuration. All tautomers are also intended to be included.

[0545] The compounds of the present disclosure, as well as their pharma- ceutically acceptable salts, hydrates, solvates, stereoisomers, and prodrugs, may exist in their tautomeric form (e.g., as an amide or imino ether). All such tautomers are contemplated herein as part of the disclosure.

[0546] The compounds of the present disclosure may contain asymmetric or chiral centers a...

Claims

1. 3-(5-(((1S,2S)-2-((2,2-difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((2,2-difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((2,2-difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((2,2-difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((2,2-difluoroethyl)(ethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(benzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(benzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(benzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(benzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(benzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1-methyloctahydrocyclopenta[b]pyrrol-6-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-methoxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-methoxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-methoxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-methoxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-methoxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-hydroxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-hydroxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-hydroxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-hydroxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-hydroxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-hydroxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-hydroxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-hydroxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-hydroxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(isobutylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(isobutylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(isobutylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(isobutylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(isobutylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4,4-difluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4,4-difluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4,4-difluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4,4-difluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(benzyloxy)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(benzyloxy)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(benzyloxy)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(benzyloxy)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(diethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(diethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-aminocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-aminocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-aminocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-aminocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(diethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(diethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(diethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-aminocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-aminocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-aminocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-aminocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-azabicyclo[3.2.1]octan-3-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-azabicyclo[3.2.1]octan-3-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-azabicyclo[3.2.1]octan-3-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-azabicyclo[3.2.1]octan-3-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-azabicyclo[3.2.1]octan-3-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 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, 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, 3-(5-((2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 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, 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, 3-(5-((2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-phenoxycyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-phenoxycyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-phenoxycyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-phenoxycyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-phenoxycyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(benzylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(benzylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(benzylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(benzylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(benzylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4S)-3-(benzylamino)tetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4S)-3-(benzylamino)tetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4R)-3-(benzylamino)tetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4R)-3-(benzylamino)tetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((3-(benzylamino)tetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(((R)-1-phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(((R)-1-phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(((R)-1-phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(((R)-1-phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(((R)-1-phenylethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(2-fluoroethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(2-fluoroethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(2-fluoroethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(2-fluoroethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(2-fluoroethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(isopropyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-methoxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-methoxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-methoxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-methoxycyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-hydroxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-hydroxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-hydroxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-hydroxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-hydroxycyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(bis(cyclopropylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(piperidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(piperidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(piperidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(piperidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(piperidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-morpholinocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-morpholinocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-morpholinocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-morpholinocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-morpholinocyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(dibenzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(dibenzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(dibenzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(dibenzylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, cis-3-(5-((2-(diethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, trans-3-(5-((2-(diethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(methylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(methylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(methylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(methylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(methylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 1-((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-methylpiperidine-4-carbonitrile, 1-((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-methylpiperidine-4-carbonitrile, 1-((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-methylpiperidine-4-carbonitrile, 1-((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-methylpiperidine-4-carbonitrile, 1-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-methylpiperidine-4-carbonitrile, 3-(5-(((1S,2S)-2-(benzyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(benzyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(benzyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(benzyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(benzyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4S)-3-aminotetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4S)-3-aminotetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4R)-3-aminotetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4R)-3-aminotetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((3-aminotetrahydro-2H-pyran-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1S,2S)-2-(benzylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1S,2R)-2-(benzylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1R,2S)-2-(benzylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(2-(benzylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4R)-4-aminotetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4R)-4-aminotetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4S)-4-aminotetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((4-aminotetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4S)-4-(diethylamino)tetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3R,4R)-4-(diethylamino)tetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4R)-4-(diethylamino)tetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((3S,4S)-4-(diethylamino)tetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((4-(diethylamino)tetrahydrofuran-3-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 3-(5-((1S,2S)-2-(diethylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1R,2S)-2-(diethylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1R,2R)-2-(diethylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((1S,2R)-2-(diethylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(2-(diethylamino)cyclobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 3-(5-(((1S,2R)-2-(ethyl((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 3-(5-((2-(ethyl((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 3-(5-(((1S,2S)-2-(isopropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(isopropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(isopropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(isopropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(isopropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 2-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 2-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 2-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 2-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 2-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)benzonitrile, 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, 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, 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, 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, 3-(5-((2-(((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-hydroxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-hydroxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-hydroxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-hydroxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-hydroxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 1-((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-(trifluoromethyl)piperidine-4-carbonitrile, 1-((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-(trifluoromethyl)piperidine-4-carbonitrile, 1-((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-(trifluoromethyl)piperidine-4-carbonitrile, 1-((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-(trifluoromethyl)piperidine-4-carbonitrile, 1-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)-4-(trifluoromethyl)piperidine-4-carbonitrile, 3-(5-(((1S,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(2,2-difluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(2,2-difluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(2,2-difluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(2,2-difluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(2,2-difluoroethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(cyclopropylmethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(cyclopropylmethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(cyclopropylmethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(cyclopropylmethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(cyclopropylmethoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(benzyloxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(benzyloxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(benzyloxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(benzyloxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(benzyloxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-isopropoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-isopropoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-isopropoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-isopropoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-isopropoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-ethoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(benzyloxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(benzyloxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(benzyloxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(benzyloxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(benzyloxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-ethoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-ethoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-ethoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-ethoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-ethoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(3,3-difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(3,3-difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(3,3-difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(3,3-difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(3,3-difluorocyclobutoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-hydroxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-hydroxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-hydroxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-hydroxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-hydroxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(4-oxopiperidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-hydroxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-hydroxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-hydroxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-hydroxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-hydroxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-hydroxy-3-methylazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-hydroxy-3-methylazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-hydroxy-3-methylazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-hydroxy-3-methylazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-hydroxy-3-methylazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(isobutylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(isobutylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(isobutylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(isobutylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(isobutylamino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione 3-(1-oxo-5-(((1S,2S)-2-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrole-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrole-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrole-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrole-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((3aR,6aS)-tetrahydro-1H-furo[3,4-c]pyrrole-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyridin-2-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyridin-2-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyridin-2-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione 3-(1-oxo-5-(((1R,2S)-2-((pyridin-2-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyridin-2-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(pyrrolidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(pyrrolidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(pyrrolidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(pyrrolidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(pyrrolidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(bis((3-methyloxetan-3-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(bis((3-methyloxetan-3-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(bis((3-methyloxetan-3-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(bis((3-methyloxetan-3-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(bis((3-methyloxetan-3-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyridin-3-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyridin-3-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyridin-3-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyridin-3-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyridin-3-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyridin-4-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyridin-4-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyridin-4-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyridin-4-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyridin-4-ylmethyl)amino)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-methoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4,4-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4,4-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4,4-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4,4-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4,4-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-methoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-methoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-methoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-methoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-methoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(oxetan-3-ylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(oxetan-3-ylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(oxetan-3-ylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(oxetan-3-ylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(oxetan-3-ylmethyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(isoindolin-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(isoindolin-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(isoindolin-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(isoindolin-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(isoindolin-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-methoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-methoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-methoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-methoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-methoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-ethoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-ethoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-ethoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-ethoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-ethoxy-4-methylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1R,4S)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((((1R,4R)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((((1R,4R)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((((1R,4S)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((((1R,4R)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, (1S,4R)-4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-carbonitrile, (1R,4r)-4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-carbonitrile, (1R,4r)-4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-carbonitrile, (1S,4r)-4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-carbonitrile, (1r,4r)-4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-carbonitrile, 4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)amino)methyl)cyclohexane-1-carbonitrile, 3-(5-(((1S,2S)-2-(((4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (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, (1R,3S)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, trans-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, cis-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclopentyl)(ethyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, 3-(5-(((1S,2S)-2-(4-fluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-fluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-fluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-fluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-fluoropiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(1,5-oxazocane-5-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(1,5-oxazocane-5-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(1,5-oxazocane-5-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(1,5-oxazocane-5-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(1,5-oxazocane-5-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3,3-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3,3-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3,3-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3,3-dimethylpiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(((1R,4S)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1R,4S)-4-methoxycyclohexyl)methyl)(methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, trans-3-(5-((2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, cis-3-(5-((2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)-4,4-dimethylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((4,4-difluorocyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((4,4-difluorocyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((4,4-difluorocyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((4,4-difluorocyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((4,4-difluorocyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((1H-indol-5-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((1H-indol-5-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((1H-indol-5-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((1H-indol-5-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((1H-indol-5-yl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-(tert-butoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-(tert-butoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-(tert-butoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-(tert-butoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(2-oxa-8-azaspiro[4.5]decan-8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(2-oxa-8-azaspiro[4.5]decan-8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(2-oxa-8-azaspiro[4.5]decan-8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(2-oxa-8-azaspiro[4.5]decan-8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(2-oxa-8-azaspiro[4.5]decan-8-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(6-azaspiro[3.5]nonan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(6-azaspiro[3.5]nonan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(6-azaspiro[3.5]nonan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(6-azaspiro[3.5]nonan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(6-azaspiro[3.5]nonan-6-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(((1S,3R)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(((1s,3S)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(((1s,3S)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(((1s,3R)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(((1s,3s)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(((1R,3S)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(((1r,3R)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(((1r,3R)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(((1r,3S)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(((1r,3r)-3-methoxycyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(8-oxa-2-azaspiro[4.5]decan-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(8-oxa-2-azaspiro[4.5]decan-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(8-oxa-2-azaspiro[4.5]decan-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(8-oxa-2-azaspiro[4.5]decan-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(8-oxa-2-azaspiro[4.5]decan-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-thiomorpholinocyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-thiomorpholinocyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-thiomorpholinocyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-thiomorpholinocyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-thiomorpholinocyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(1,4-oxazepan-4-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(1,4-oxazepan-4-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(1,4-oxazepan-4-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(1,4-oxazepan-4-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(1,4-oxazepan-4-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-isopropoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-isopropoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-isopropoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-isopropoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-isopropoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-(cyclopropylmethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-(cyclopropylmethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-(cyclopropylmethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-(cyclopropylmethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-(cyclopropylmethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 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, 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, 3-(5-((2-((3aR,4R,7S,7aS)-octahydro-2H-4,7-epoxyisoindol-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-ethoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-ethoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-ethoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-ethoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-ethoxypiperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1S,4R)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((((1s,4S)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((((1s,4S)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((((1s,4R)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((((1s,4s)-4-methoxycyclohexyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((R)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((R)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((R)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((R)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((R)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((S)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((S)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((S)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((S)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((S)-3-methoxypyrrolidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((3,3-difluorocyclobutyl)methyl)amino)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-(difluoromethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-(difluoromethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-(difluoromethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-(difluoromethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-(difluoromethoxy)piperidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 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, 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, 3-(5-((2-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(propylamino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(propylamino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(propylamino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(propylamino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(propylamino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(dipropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(dipropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(dipropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(dipropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(dipropylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyridin-4-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyridin-4-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyridin-4-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyridin-4-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyridin-4-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyridin-3-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((1-ethyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((1-ethyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((1-ethyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((1-ethyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((1-ethyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((1-isopropyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((1-isopropyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((1-isopropyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((1-isopropyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((1-isopropyl-1H-pyrazol-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethyl(methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(dimethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(dimethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(dimethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(dimethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(dimethylamino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((oxetan-3-ylmethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((oxetan-3-ylmethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((oxetan-3-ylmethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((oxetan-3-ylmethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((oxetan-3-ylmethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((2-hydroxyethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((2-hydroxyethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((2-hydroxyethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((2-hydroxyethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((2-hydroxyethyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(pyrrolidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(pyrrolidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(pyrrolidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(pyrrolidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(pyrrolidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-morpholinocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-morpholinocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-morpholinocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-morpholinocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-morpholinocyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyridin-2-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyridin-2-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyridin-2-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyridin-2-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyridin-2-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((3-hydroxy-3-methylbutyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((3-hydroxy-3-methylbutyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((3-hydroxy-3-methylbutyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((3-hydroxy-3-methylbutyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((3-hydroxy-3-methylbutyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((3-methyloxetan-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((3-methyloxetan-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((3-methyloxetan-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((3-methyloxetan-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((3-methyloxetan-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-methoxy-4-methylpiperidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-methoxy-4-methylpiperidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-methoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-methoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-methoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-methoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-methoxyazetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((6-methylpyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((6-methylpyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((6-methylpyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((6-methylpyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((6-methylpyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((5-methoxypyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((5-methoxypyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((5-methoxypyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((5-methoxypyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((5-methoxypyridin-2-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((6-methoxypyridin-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((6-methoxypyridin-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((6-methoxypyridin-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((6-methoxypyridin-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((6-methoxypyridin-3-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, 3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, 3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, 3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, 3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1S,3R)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1R,3R)-3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1R,3R)-3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1S,3r)-3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1r,3r)-3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1R,3S)-3-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1S,3s)-3-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1S,3s)-3-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1R,3s)-3-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, (1s,3s)-3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)-1-methylcyclobutane-1-carbonitrile, 3-(1-oxo-5-(((1S,2S)-2-(piperidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(piperidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(piperidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(piperidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(piperidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1S,3R)-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((((1s,3S)-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((((1s,3S)-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((((1s,3R)-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((((1s,3s)-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((cis-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((cis-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((cis-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((cis-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((cis-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1R,3S)-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((trans-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((trans-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((trans-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((trans-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((trans-3-methoxycyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1r,4S)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((((1r,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((((1r,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((((1r,4S)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((((1r,4r)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyrimidin-5-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyrimidin-5-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyrimidin-5-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyrimidin-5-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyrimidin-5-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((4-methoxytetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((4-methoxytetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((4-methoxytetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((4-methoxytetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((4-methoxytetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((7-oxaspiro[3.5]nonan-2-yl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((7-oxaspiro[3.5]nonan-2-yl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((7-oxaspiro[3.5]nonan-2-yl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((7-oxaspiro[3.5]nonan-2-yl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((7-oxaspiro[3.5]nonan-2-yl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 1-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-carbonitrile, 1-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-carbonitrile, 1-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-carbonitrile, 1-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-carbonitrile, 1-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)cyclobutane-1-carbonitrile, 3-(5-(((1S,2S)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(2-chlorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(2-methoxyphenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-((pyrazolo[1,5-a]pyrimidin-6-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-((pyrazolo[1,5-a]pyrimidin-6-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-((pyrazolo[1,5-a]pyrimidin-6-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-((pyrazolo[1,5-a]pyrimidin-6-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-((pyrazolo[1,5-a]pyrimidin-6-ylmethyl)amino)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((2,4-difluorobenzyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((2,4-difluorobenzyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((2,4-difluorobenzyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((2,4-difluorobenzyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((2,4-difluorobenzyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((1R,2R)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((1R,2R)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((1R,2R)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((1R,2R)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((1R,2R)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((1S,2S)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((1S,2S)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((1S,2S)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((1S,2S)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((1S,2S)-2-methoxycyclopentyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 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, 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, 3-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)amino)methyl)bicyclo[1.1.1]pentane-1-carbonitrile, 3-(5-(((1S,2S)-2-(3-(3-fluorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-(3-fluorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-(3-fluorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-(3-fluorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-(3-fluorophenoxy)azetidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1S,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((((1s,4S)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((((1s,4S)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((((1s,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((((1s,4s)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((cis-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((trans-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(bis(((1R,4S)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(bis(((1r,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(bis(((1r,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(bis(((1r,4S)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(bis(((1r,4R)-4-methoxycyclohexyl)methyl)amino)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 4-((((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)(methyl)amino)methyl)benzonitrile, 4-((((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)(methyl)amino)methyl)benzonitrile, 4-((((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)(methyl)amino)methyl)benzonitrile, 4-((((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)(methyl)amino)methyl)benzonitrile, 4-(((2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oxy)cyclohexyl)(methyl)amino)methyl)benzonitrile, 3-(5-((2-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(ethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(ethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(ethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(ethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(ethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(benzylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(benzylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(benzylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(benzylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(benzylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(diethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(diethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(diethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(diethylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(4-methoxy-4-methylpiperidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(4-methoxy-4-methylpiperidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(4-methoxy-4-methylpiperidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(4-methoxy-4-methylpiperidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(4-methoxy-4-methylpiperidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(isobutylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(isobutylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(isobutylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(isobutylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(isobutylamino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(propylamino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(propylamino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(propylamino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(propylamino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(propylamino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-((((1R,4S)-4-methoxycyclohexyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-((((1r,4R)-4-methoxycyclohexyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-((((1r,4R)-4-methoxycyclohexyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-((((1r,4S)-4-methoxycyclohexyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-((((1r,4r)-4-methoxycyclohexyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cycloheptyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((3-methyloxetan-3-yl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((3-methyloxetan-3-yl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((3-methyloxetan-3-yl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((3-methyloxetan-3-yl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((3-methyloxetan-3-yl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 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, 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, 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, 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, 3-(5-((2-(((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-methoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-methoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-methoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-methoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-methoxyazetidin-1-yl)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(((3,3-difluorocyclobutyl)methyl)amino)cycloheptyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(diethylamino)-3-methylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)-3-methylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(diethylamino)-3-methylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(diethylamino)-3-methylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(diethylamino)-3-methylcyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(3-(pyridazin-3-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(3-(pyridazin-3-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(3-(pyridazin-3-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(3-(pyridazin-3-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(3-(pyridazin-3-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(3-isopropoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(3-isopropoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(3-isopropoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(3-isopropoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(3-isopropoxyazetidin-1-yl)cyclopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(3-(2,2,2-trifluoroethoxy)azetidin-1-yl)cyclopentyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S,3S,4R)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S,3R,4R)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R,3R,4R)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R,3S,4R)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,4R)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S,3S,4S)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S,3R,4S)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R,3R,4S)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R,3S,4S)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,4S)-3-(3-ethoxyazetidin-1-yl)bicyclo[2.2.1]heptan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2S)-2-(3-(pyrazin-2-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1S,2R)-2-(3-(pyrazin-2-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2R)-2-(3-(pyrazin-2-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-(((1R,2S)-2-(3-(pyrazin-2-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(1-oxo-5-((2-(3-(pyrazin-2-yloxy)azetidin-1-yl)cyclohexyl)oxy)isoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-aminocyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-aminocyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-aminocyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-aminocyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-aminocyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)cyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(diethylamino)cyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(diethylamino)cyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(diethylamino)cyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-(diethylamino)cyclopentyl)oxy)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-aminocyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-aminocyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-aminocyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-aminocyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-((2-aminocyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2S)-2-(diethylamino)cyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1S,2R)-2-(diethylamino)cyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2R)-2-(diethylamino)cyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione, 3-(5-(((1R,2S)-2-(diethylamino)cyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(5-((2-(diethylamino)cyclopentyl)oxy)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A compound selected from or pharma- ceutically acceptable salts, hydrates, solvates, stereoisomers, and tautomers thereof.

2. 13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier or excipient.

3. 3. The pharmaceutical composition of claim 2, further comprising at least one additional pharmaceutical agent.

4. 4. A pharmaceutical composition according to claim 2 or 3 for use in the treatment of a disease or disorder affected by reduced IKZF2 protein levels.

5. 10. A pharmaceutical composition for degrading IKZF2, comprising the compound of claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof.

6. A pharmaceutical composition for treating a disease or disorder affected by modulation of IKZF2 protein levels, comprising a compound of claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof.

7. 10. A pharmaceutical composition for modulating IKZF2 protein levels, comprising a compound according to claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof.

8. A pharmaceutical composition for a method of reducing cell proliferation, comprising a compound described in claim 1, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, said method comprising contacting the compound described in claim 1, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, with the cell, and reducing IKZF2 protein levels.

9. 13. A pharmaceutical composition for treating cancer, comprising a compound of claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

10. 10. The pharmaceutical composition of claim 9, wherein the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid leukemia and gastrointestinal stromal tumor (GIST).

11. The pharmaceutical composition according to claim 9, wherein the cancer is an immune response deficient cancer or an immunogenic cancer.

12. A pharmaceutical composition for a method of reducing IKZF2 protein levels in a subject, comprising the compound of claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

13. The pharmaceutical composition according to any one of claims 5 to 12, wherein the administration is carried out orally, parenterally, subcutaneously, by injection or infusion.

14. 2. A compound according to claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof for use in the treatment of a disease or disorder affected by reduced IKZF2 protein levels.

15. 2. Use of a compound of claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof in the manufacture of a medicament for treating a disease or disorder affected by reduced IKZF2 protein levels.

16. 2. A compound according to claim 1 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof for use in the manufacture of a medicament for treating a disease or disorder associated with decreased IKZF2 protein levels.

17. 17. The compound of claim 16, wherein the disease or disorder is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite-stable colorectal cancer (mssCRC), thymoma, carcinoid, acute myeloid leukemia and gastrointestinal stromal tumor (GIST).

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